Corinne L. Fligner

It has been suggested that limiting access to firearms could prevent many suicides, but this belief is controversial. To assess the strength of the association between the availability of firearms and suicide, we studied all suicides that took place in the homes of victims in Shelby County, Tennessee, and King County, Washington, over a 32-month period.

OBJECTIVE: The purpose of this study was to determine whether gadolinium (Gd) is deposited in brain and bone tissues in patients receiving only non-Group 1 agents, either macrocyclic or linear protein interacting Gd-based contrast agents, with normal renal function. Group 1 agents are linear agents most associated with nephrogenic systemic fibrosis that the US Federal Drug Administration has defined as contraindicated in patients at risk for this disease. MATERIALS AND METHODS: This study was institutional review board approved and Health Insurance Portability and Accountability Act compliant for retrospective review of records and also had signed autopsy consent authorizing use of decedent's tissue in research studies. Tissue samples were collected from 9 decedents undergoing autopsy who had contrast-enhanced magnetic resonance imaging (MRI) with only single agent exposure to a non-Group 1 Gd-based contrast agent. Decedents with only noncontrast MRI or no MRI served as controls. Multiple brain areas, including globus pallidus and dentate nucleus, as well as bone and skin, were sampled and analyzed for Gd using inductively coupled plasma mass spectrometry. Gadolinium levels were compared between groups of decedents using the Mann-Whitney test and between brain and bone tissues of the same cases using the Wilcoxon signed-rank test. RESULTS: Of the 9 decedents, 5 received gadoteridol (ProHance; Bracco Diagnostics, Princeton, NJ), 2 received gadobutrol (Gadovist; Bayer Healthcare, Whippany, NJ), and 1 each had gadobenate (MultiHance; Bracco Diagnostics) and gadoxetate (Eovist; Bayer Healthcare). Gadolinium was found with all agents in all brain areas sampled with highest levels in globus pallidus and dentate. Bone levels measured 23 times higher (median) than brain levels (P = 0.008 for bone vs globus pallidus) and showed a significant correlation (r = 0.81, P = 0.022). In controls, Gd levels in the brain were at or below limits of measurement and were significantly lower compared with study cases (P = 0.005 for globus pallidus). CONCLUSION: Gadolinium deposition in normal brain and bone tissue occurs with macrocyclic and linear protein interacting agents in patients with normal renal function. Deposition of Gd in cortical bone occurs at much higher levels compared with brain tissue and shows a notable correlation between the two. Thus, the bone may serve as a surrogate to estimate brain deposition if brain Gd were to become a useful clinical or research marker.

The diaphragm is the primary muscle of ventilation. Dysfunction of the diaphragm is an underappreciated cause of respiratory difficulties and may be due to a wide variety of entities, including surgery, trauma, tumor, and infection. Diaphragmatic disease usually manifests as elevation at chest radiography. Functional imaging with fluoroscopy (or ultrasonography or magnetic resonance imaging) is a simple and effective method of diagnosing diaphragmatic dysfunction, which can be classified as paralysis, weakness, or eventration. Diaphragmatic paralysis is indicated by absence of orthograde excursion on quiet and deep breathing, with paradoxical motion on sniffing. Diaphragmatic weakness is indicated by reduced or delayed orthograde excursion on deep breathing, with or without paradoxical motion on sniffing. Eventration is congenital thinning of a segment of diaphragmatic muscle and manifests as focal weakness. Treatment of diaphragmatic paralysis depends on the cause of the dysfunction and the severity of the symptoms. Treatment options include plication and phrenic nerve stimulation. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.322115127/-/DC1.

Amyloid deposition and reduced β-cell mass are pathological hallmarks of the pancreatic islet in type 2 diabetes; however, whether the extent of amyloid deposition is associated with decreased β-cell mass is debated. We investigated the possible relationship and, for the first time, determined whether increased islet amyloid and/or decreased β-cell area quantified on histological sections is correlated with increased β-cell apoptosis. Formalin-fixed, paraffin-embedded human pancreas sections from subjects with (n = 29) and without (n = 39) diabetes were obtained at autopsy (64 ± 2 and 70 ± 4 islets/subject, respectively). Amyloid and β cells were visualized by thioflavin S and insulin immunolabeling. Apoptotic β cells were detected by colabeling for insulin and by TUNEL. Diabetes was associated with increased amyloid deposition, decreased β-cell area, and increased β-cell apoptosis, as expected. There was a strong inverse correlation between β-cell area and amyloid deposition (r = −0.42, P < 0.001). β-Cell area was selectively reduced in individual amyloid-containing islets from diabetic subjects, compared with control subjects, but amyloid-free islets had β-cell area equivalent to islets from control subjects. Increased amyloid deposition was associated with β-cell apoptosis (r = 0.56, P < 0.01). Thus, islet amyloid is associated with decreased β-cell area and increased β-cell apoptosis, suggesting that islet amyloid deposition contributes to the decreased β-cell mass that characterizes type 2 diabetes. Amyloid deposition and reduced β-cell mass are pathological hallmarks of the pancreatic islet in type 2 diabetes; however, whether the extent of amyloid deposition is associated with decreased β-cell mass is debated. We investigated the possible relationship and, for the first time, determined whether increased islet amyloid and/or decreased β-cell area quantified on histological sections is correlated with increased β-cell apoptosis. Formalin-fixed, paraffin-embedded human pancreas sections from subjects with (n = 29) and without (n = 39) diabetes were obtained at autopsy (64 ± 2 and 70 ± 4 islets/subject, respectively). Amyloid and β cells were visualized by thioflavin S and insulin immunolabeling. Apoptotic β cells were detected by colabeling for insulin and by TUNEL. Diabetes was associated with increased amyloid deposition, decreased β-cell area, and increased β-cell apoptosis, as expected. There was a strong inverse correlation between β-cell area and amyloid deposition (r = −0.42, P < 0.001). β-Cell area was selectively reduced in individual amyloid-containing islets from diabetic subjects, compared with control subjects, but amyloid-free islets had β-cell area equivalent to islets from control subjects. Increased amyloid deposition was associated with β-cell apoptosis (r = 0.56, P < 0.01). Thus, islet amyloid is associated with decreased β-cell area and increased β-cell apoptosis, suggesting that islet amyloid deposition contributes to the decreased β-cell mass that characterizes type 2 diabetes. Type 2 diabetes is characterized by insulin resistance and β-cell failure,1Kahn S.E. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes.Diabetologia. 2003; 46: 3-19Crossref PubMed Google Scholar the latter resulting from reductions in β-cell function2Brunzell J.D. Robertson R.P. Lerner R.L. Hazzard W.R. Ensinck J.W. Bierman E.L. Porte Jr, D. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests.J Clin Endocrinol Metab. 1976; 42: 222-229Crossref PubMed Scopus (413) Google Scholar, 3Jensen C.C. Cnop M. Hull R.L. Fujimoto W.Y. Kahn SE; American Diabetes Association GENNID Study Group Beta-cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the U.S.Diabetes. 2002; 51: 2170-2178Crossref PubMed Scopus (267) Google Scholar and/or β-cell mass.4Klöppel G. Löhr M. Habich K. Oberholzer M. Heitz P.U. Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited.Surv Synth Pathol Res. 1985; 4: 110-125PubMed Google Scholar, 5Butler A.E. Janson J. Bonner-Weir S. Ritzel R. Rizza R.A. Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.Diabetes. 2003; 52: 102-110Crossref PubMed Scopus (3196) Google Scholar, 6Rahier J. Guiot Y. Goebbels R.M. Sempoux C. Henquin J.C. Pancreatic beta-cell mass in European subjects with type 2 diabetes.Diabetes Obes Metab. 2008; 10: 32-42Crossref PubMed Scopus (546) Google Scholar Together, these contribute to impaired insulin release and the inability to maintain euglycemia without glucose-lowering therapy. A pathological hallmark of the pancreatic islet in type 2 diabetes is islet amyloid deposition. These deposits occur in the majority of patients with diabetes,5Butler A.E. Janson J. Bonner-Weir S. Ritzel R. Rizza R.A. Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.Diabetes. 2003; 52: 102-110Crossref PubMed Scopus (3196) Google Scholar, 7Westermark P. Quantitative studies on amyloid in the islets of Langerhans.Ups J Med Sci. 1972; 77: 91-94Crossref PubMed Scopus (137) Google Scholar, 8Clark A. Wells C.A. Buley I.D. Cruickshank J.K. Vanhegan R.I. Matthews D.R. Cooper G.J. Holman R.R. Turner R.C. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.Diabetes Res. 1988; 9: 151-159PubMed Google Scholar, 9Sakuraba H. Mizukami H. Yagihashi N. Wada R. Hanyu C. Yagihashi S. Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients.Diabetologia. 2002; 45: 85-96Crossref PubMed Scopus (517) Google Scholar, 10Zhao H.L. Lai F.M. Tong P.C. Zhong D.R. Yang D. Tomlinson B. Chan J.C. Prevalence and clinicopathological characteristics of islet amyloid in Chinese patients with type 2 diabetes.Diabetes. 2003; 52: 2759-2766Crossref PubMed Scopus (91) Google Scholar but have also been reported in a small proportion of subjects who are apparently nondiabetic (but may have undiagnosed abnormalities in glucose metabolism), and especially in those who are older.7Westermark P. Quantitative studies on amyloid in the islets of Langerhans.Ups J Med Sci. 1972; 77: 91-94Crossref PubMed Scopus (137) Google Scholar, 11Bell E.T. Hyalinization of the islets of Langerhans in nondiabetic individuals.Am J Pathol. 1959; 35: 801-805PubMed Google Scholar The formation of islet amyloid occurs by aggregation of islet amyloid polypeptide (IAPP, or amylin),12Westermark P. Wernstedt C. Wilander E. Hayden D.W. O'Brien T.D. Johnson K.H. Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells.Proc Natl Acad Sci USA. 1987; 84: 3881-3885Crossref PubMed Scopus (864) Google Scholar, 13Cooper G.J.S. Willis A.C. Clark A. Turner R.C. Sim R.B. Reid K.B.M. Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients.Proc Natl Acad Sci USA. 1987; 84: 8628-8632Crossref PubMed Scopus (1155) Google Scholar which is normally cosecreted with insulin by the β cell.14Kahn S.E. D'Alessio D.A. Fujimoto W.Y. Ensinck J.W. Jr, G.J. Porte Jr, D. of of islet amyloid polypeptide and insulin by PubMed Scopus Google Scholar studies have that the of aggregation is resulting in β-cell A. B. Pancreatic islet of associated with diabetes PubMed Scopus Google Scholar, J. D. S. Butler P.C. The of islet amyloid polypeptide is by amyloid PubMed Scopus Google Scholar studies of islet amyloid deposition in and in Jr, studies on the of diabetes in individual PubMed Scopus Google Scholar, Clark A. Diabetes mellitus in is by islet and in beta-cell PubMed Scopus Google Scholar, R. A. J. C. G. C. S. C. G. A. R.A. Pancreatic islet beta-cell apoptosis, and are of islet in diabetic Natl Acad Sci USA. PubMed Scopus Google Scholar, Johnson K.H. O'Brien T.D. P. Quantitative of islet amyloid polypeptide in impaired glucose and diabetic PubMed Scopus Google Scholar as as in of islet amyloid Hull R.L. J. Cnop M. Kahn S.E. Islet amyloid the pancreas and PubMed Scopus Google Scholar, R.L. S. J. Cnop M. R.L. Kahn S.E. Increased islet amyloid formation and beta-cell dysfunction in a of islet 2003; 52: PubMed Scopus Google Scholar, J. K. Hull R.L. S. K. Tong J. J. Kahn S.E. Amyloid formation in of of human 52: PubMed Scopus Google Scholar have that the of islet amyloid formation fasting and is associated with decreased β-cell function and β-cell studies the relationship between β-cell mass and islet amyloid are studies have β-cell area and islet amyloid deposition in histological sections from the human pancreas A.E. Janson J. Bonner-Weir S. Ritzel R. Rizza R.A. Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.Diabetes. 2003; 52: 102-110Crossref PubMed Scopus (3196) Google Scholar, 8Clark A. Wells C.A. Buley I.D. Cruickshank J.K. Vanhegan R.I. Matthews D.R. Cooper G.J. Holman R.R. Turner R.C. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.Diabetes Res. 1988; 9: 151-159PubMed Google Scholar, 9Sakuraba H. Mizukami H. Yagihashi N. Wada R. Hanyu C. Yagihashi S. Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients.Diabetologia. 2002; 45: 85-96Crossref PubMed Scopus (517) Google Scholar, P. The pancreatic islet cells in in human diabetic and Pathol A. Google Scholar, S. M. N. A. E. B. B. A. F.M. and abnormalities in the islets from type 2 diabetic PubMed Scopus Google Scholar studies have of between these however, and the are A. Wells C.A. Buley I.D. Cruickshank J.K. Vanhegan R.I. Matthews D.R. Cooper G.J. Holman R.R. Turner R.C. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.Diabetes Res. 1988; 9: 151-159PubMed Google Scholar, P. The pancreatic islet cells in in human diabetic and Pathol A. Google Scholar a correlation between increased amyloid deposition and β-cell P. The pancreatic islet cells in in human diabetic and Pathol A. Google Scholar but the that relationship A. Wells C.A. Buley I.D. Cruickshank J.K. Vanhegan R.I. Matthews D.R. Cooper G.J. Holman R.R. Turner R.C. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.Diabetes Res. 1988; 9: 151-159PubMed Google Scholar of these studies whether the of β cells occurs selectively in islets and whether islet amyloid deposition, or changes in β-cell area, are associated with increased β-cell apoptosis and/or decreased β-cell the present to the relationship between islet amyloid deposition and decreased β-cell area in humans and to for the first time, whether islet amyloid deposition is associated with increased β-cell apoptosis and/or reduced β-cell We patients with by type 2 diabetes in with or without the of We also nondiabetic control subjects who these and who had a glucose of with a of pancreatic or were The was by at the of and the Pancreatic was obtained during at the of and the were from the of the however, autopsy from of the the pancreas had been were in the or by Pancreatic was are as β-cell area, β-cell Formalin-fixed, paraffin-embedded pancreas were sections and sections were sections were with insulin at or at to β cells and were with thioflavin S to amyloid with to or with at to for insulin were or of by were from sections were with to were on islets a of pancreas of the The was to the diabetes of The of islets was ± 2 in diabetic subjects and 70 ± 4 in the control = the area of the sections ± ± diabetes P = islet ± ± diabetes P = between Islet area was by islet by characteristics of the on the thioflavin S and the area of that of The for islet was area and thioflavin area were determined a quantitative as Hull R.L. J. Cnop M. Kahn S.E. Islet amyloid the pancreas and PubMed Scopus Google Scholar, R.L. K. R.L. Kahn S.E. in in but increased insulin for of impaired PubMed Scopus Google Scholar Amyloid was as the of islets amyloid by the of amyloid as amyloid area by the islet area and β-cell area as area or as area by the islet area β-cell area, were as of β-cell apoptosis and was in a of for a in apoptosis with to that in A.E. Janson J. Bonner-Weir S. Ritzel R. Rizza R.A. Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.Diabetes. 2003; 52: 102-110Crossref PubMed Scopus (3196) Google Scholar a of subjects β-Cell apoptosis was on sections from control subjects and diabetic subjects of ± and ± islet for β-cell sections from control subjects and diabetic subjects were of ± and ± islet respectively). The characteristics of these subjects and histological of islet area, islet amyloid deposition, and β-cell area in from β-Cell apoptosis and were as the of or β cells to area, to A.E. Janson J. Bonner-Weir S. Ritzel R. Rizza R.A. Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.Diabetes. 2003; 52: 102-110Crossref PubMed Scopus (3196) Google Scholar The for β cells was to the for β cells was to that for β-cell and insulin cells were in of these however, cells were in islet cells or in exocrine that was a of β cells and a of the islet from islets of diabetic subjects (n = were compared with those of the control subjects (n = and whether was a in islet area and β-cell area between and from individual islet from diabetic subjects were as amyloid (n = or (n = Islet area and β-cell area were determined and compared with islets in control subjects (n = and with those islets from control subjects that were amyloid (n = for that were normally are reported as ± for characteristics and ± for are as and were or of with normal or were compared a that were normally a was were correlation with or without for diabetes and of A was to the in for between the diabetes and control A P of was Group characteristics are in 1 and characteristics for individual subjects are in were for and those with diabetes were glucose levels of diabetic subjects were control subjects. The of diabetes was The of diabetic subjects with oral or insulin are reported in subjects were with a of insulin and were for the as insulin The of between the of and Diabetes 2 characteristics = = ± ± ± ± glucose ± ± Diabetes were for ± of are reported as ± mass Diabetes were for subjects. in a of glucose of in in a are reported as ± mass control for the in mass between a of subjects (n = were by for in ± ± for diabetic control and ± ± glucose levels were in diabetic subjects in ± ± P < 0.001). The characteristics in these between the groups and were from those of the of with diabetes islet amyloid deposition amyloid was also present in of the nondiabetic control subjects, amyloid and were in diabetic subjects and the of subjects for islet amyloid and were in diabetic subjects ± ± and ± ± P < for the islet amyloid and were in subjects and in diabetic subjects (r = P < 0.001). Islet amyloid was correlated with in subjects (r = P = and in diabetic subjects (r = P = amyloid amyloid was associated with diabetes or diabetes that islet amyloid was detected in a proportion of control subjects, whether characteristics were associated with the of amyloid deposition in control subjects with islet amyloid from those without islet amyloid in of or The of islet was however, the was between groups A and a islet area = islet area in the of subjects for = and islet area with in the (r = P = with type 2 diabetes had a β-cell area, compared with control subjects < β-Cell area in the diabetic to islet area < the of subjects for β-cell area and area were in with diabetes and ± ± P < for the was inverse relationship between islet amyloid and β-cell area (r = −0.42, P < and β-cell area (r = P < with these were for the for of β-cell area (r = P < for β-cell = P < for β-cell for diabetes and of the between islet amyloid and β-cell area and β-cell area < for the control was between islet amyloid and β-cell area (r = P = for β-cell area and = P = for β-cell Islet amyloid was also correlated with β-cell area (r = P < for the = P = for diabetic and was correlated with decreased β-cell area (r = P < for the = P < for diabetic the control was between islet amyloid and β-cell area (r = P = for β-cell area and = P = for β-cell the relationship between amyloid deposition and reduced β-cell area, determined whether of β-cell area selectively in from islets from diabetic as amyloid (n = or amyloid (n = were compared with control islets (n = islets from diabetic subjects were islets without amyloid < and area was reduced in islets < There was in area between islets from diabetic subjects and islets from control subjects = from the islets obtained from the with diabetes were compared with control islets (n = the were the to whether the increased islet amyloid and decreased β-cell area in with diabetes was associated with changes in β-cell apoptosis or A and The of β-cell apoptosis in diabetic subjects was that for control subjects < the of β-cell was between groups = the of for β-cell apoptosis was in diabetic subjects ± ± = and P < with in β-cell ± ± = and P = the increased amyloid was associated with β-cell apoptosis (r = 0.56, P < and to associated with increased β-cell apoptosis in diabetic subjects (r = P = β-cell apoptosis was associated with β-cell area, in subjects (r = P = and in those with diabetes (r = P < these correlation β-cell area was the β-cell apoptosis the β-cell area We have that in type 2 diabetes the of amyloid in islets is associated with decreased β-cell human studies relationship A. Wells C.A. Buley I.D. Cruickshank J.K. Vanhegan R.I. Matthews D.R. Cooper G.J. Holman R.R. Turner R.C. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.Diabetes Res. 1988; 9: 151-159PubMed Google Scholar, P. The pancreatic islet cells in in human diabetic and Pathol A. Google Scholar We that to the that β-cell area is reduced in islets from diabetic subjects, the of amyloid in the of β cells in is the first to the relationship between amyloid deposition and β-cell apoptosis. We in with A.E. Janson J. Bonner-Weir S. Ritzel R. Rizza R.A. Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.Diabetes. 2003; 52: 102-110Crossref PubMed Scopus (3196) Google Scholar that β-cell apoptosis was increased in subjects with type 2 diabetes. and for the first time, that β-cell apoptosis is associated with increased islet amyloid and decreased β-cell Islet amyloid was present to in of with in with A.E. Janson J. Bonner-Weir S. Ritzel R. Rizza R.A. Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.Diabetes. 2003; 52: 102-110Crossref PubMed Scopus (3196) Google Scholar, 7Westermark P. Quantitative studies on amyloid in the islets of Langerhans.Ups J Med Sci. 1972; 77: 91-94Crossref PubMed Scopus (137) Google Scholar, 8Clark A. Wells C.A. Buley I.D. Cruickshank J.K. Vanhegan R.I. Matthews D.R. Cooper G.J. Holman R.R. Turner R.C. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.Diabetes Res. 1988; 9: 151-159PubMed Google Scholar Increased islet amyloid was associated with in the and the diabetes with the of amyloid islet amyloid deposition area was to diabetes however, on diabetes were in subjects, and the is that diabetes undiagnosed for of Thus, is that a relationship between these studies have a of islet amyloid in control A. Wells C.A. Buley I.D. Cruickshank J.K. Vanhegan R.I. Matthews D.R. Cooper G.J. Holman R.R. Turner R.C. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.Diabetes Res. 1988; 9: 151-159PubMed Google Scholar, S. M. N. A. E. B. B. A. F.M. and abnormalities in the islets from type 2 diabetic PubMed Scopus Google Scholar the present however, detected amyloid in at islet in of nondiabetic subjects, in with P. Quantitative studies on amyloid in the islets of Langerhans.Ups J Med Sci. 1972; 77: 91-94Crossref PubMed Scopus (137) Google Scholar, 11Bell E.T. Hyalinization of the islets of Langerhans in nondiabetic individuals.Am J Pathol. 1959; 35: 801-805PubMed Google Scholar islet amyloid deposition been in subjects without P. Quantitative studies on amyloid in the islets of Langerhans.Ups J Med Sci. 1972; 77: 91-94Crossref PubMed Scopus (137) Google Scholar, 11Bell E.T. Hyalinization of the islets of Langerhans in nondiabetic individuals.Am J Pathol. 1959; 35: 801-805PubMed Google Scholar to a relationship between amyloid and in control subjects. of correlation may to the small of subjects with amyloid in We also a in β-cell area in with compared with control subjects, which is the reported G. Löhr M. Habich K. Oberholzer M. Heitz P.U. Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited.Surv Synth Pathol Res. 1985; 4: 110-125PubMed Google Scholar, 5Butler A.E. Janson J. Bonner-Weir S. Ritzel R. Rizza R.A. Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.Diabetes. 2003; 52: 102-110Crossref PubMed Scopus (3196) Google Scholar, 6Rahier J. Guiot Y. Goebbels R.M. Sempoux C. Henquin J.C. Pancreatic beta-cell mass in European subjects with type 2 diabetes.Diabetes Obes Metab. 2008; 10: 32-42Crossref PubMed Scopus (546) Google Scholar, 8Clark A. Wells C.A. Buley I.D. Cruickshank J.K. Vanhegan R.I. Matthews D.R. Cooper G.J. Holman R.R. Turner R.C. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.Diabetes Res. 1988; 9: 151-159PubMed Google Scholar, 9Sakuraba H. Mizukami H. Yagihashi N. Wada R. Hanyu C. Yagihashi S. Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients.Diabetologia. 2002; 45: 85-96Crossref PubMed Scopus (517) Google Scholar The of β-cell reported in diabetes between and studies may to the in β-cell area in control subjects and subjects with type 2 J. Guiot Y. Goebbels R.M. Sempoux C. Henquin J.C. Pancreatic beta-cell mass in European subjects with type 2 diabetes.Diabetes Obes Metab. 2008; 10: 32-42Crossref PubMed Scopus (546) Google Scholar, 9Sakuraba H. Mizukami H. Yagihashi N. Wada R. Hanyu C. Yagihashi S. Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients.Diabetologia. 2002; 45: 85-96Crossref PubMed Scopus (517) Google Scholar which also in We a inverse relationship between the of islet amyloid deposition and of β-cell area in with to of the in β-cell area by amyloid deposition. the that β-cell area in islets from diabetes and control subjects was but β-cell area was reduced in islets from diabetes subjects. a for islet amyloid formation in the of β cells that is in the pathogenesis of type 2 diabetes. formation been to in β-cell apoptosis in cells and as as in pancreas from A. B. Pancreatic islet of associated with diabetes PubMed Scopus Google Scholar, J. D. S. Butler P.C. The of islet amyloid polypeptide is by amyloid PubMed Scopus Google Scholar, J. K. Hull R.L. S. K. Tong J. J. Kahn S.E. Amyloid formation in of of human 52: PubMed Scopus Google Scholar, A.E. Janson J. Butler P.C. Increased beta-cell apoptosis in beta-cell mass in of type 2 for of islet amyloid formation of 2003; 52: PubMed Scopus Google Scholar, A. Oberholzer J. of amyloid polypeptide expression islet amyloid formation and of human islets in 2008; PubMed Scopus Google Scholar, S. Hull R.L. J. K. R. Kahn S.E. is by islet amyloid formation and 52: PubMed Scopus Google Scholar, M. Amyloid of human PubMed Scopus Google Scholar of islet amyloid formation in decreased β-cell apoptosis in S. Hull R.L. J. K. R. Kahn S.E. is by islet amyloid formation and 52: PubMed Scopus Google Scholar and human A. Oberholzer J. of amyloid polypeptide expression islet amyloid formation and of human islets in 2008; PubMed Scopus Google Scholar, M. Amyloid of human PubMed Scopus Google Scholar a between amyloid formation and β-cell apoptosis. with a A.E. Janson J. Bonner-Weir S. Ritzel R. Rizza R.A. Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.Diabetes. 2003; 52: 102-110Crossref PubMed Scopus (3196) Google Scholar β-cell apoptosis to increased in type 2 diabetes. that increased islet amyloid in subjects was associated with increased β-cell apoptosis, suggesting that the of amyloid deposition may also of β-cell in correlation was the diabetes was may to the of subjects for which β-cell apoptosis was to the amyloid deposits detected in the present by thioflavin S may also contribute to β-cell in diabetes. studies that of during the of amyloid deposition the amyloid deposits are and β-cell J. D. S. Butler P.C. The of islet amyloid polypeptide is by amyloid PubMed Scopus Google Scholar or of have been reported to present in β cells from subjects with type 2 H.L. Y. J. Lai F.M. Tong P.C. Chan J.C. Amyloid in diabetic and nondiabetic human Res. PubMed Scopus Google Scholar, S. O'Brien T.D. Butler P.C. for in cells in type 2 islet amyloid polypeptide in the J Pathol. PubMed Scopus Google Scholar and are to the of in the present that islets from diabetic subjects have reduced β-cell area relative to those from nondiabetic control subjects. Thus, small of were present in islets from diabetic subjects, to have in β-cell and as have in a S. Hull R.L. Clark A. Kahn S.E. and islet by or by PubMed Scopus Google Scholar the to these small for in human pancreas and and have to A of the present is that diabetes was determined from a is possible that subjects, or that subjects with insulin may have had type 1 diabetes. however, have to the relationship between islet amyloid deposition and β-cell area that in of is that the of the pancreas was in sections of the pancreas may have in or of the of islet amyloid deposition. were to between the of of studies on human and human pancreas have that amyloid the A. Wells C.A. Buley I.D. Cruickshank J.K. Vanhegan R.I. Matthews D.R. Cooper G.J. Holman R.R. Turner R.C. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.Diabetes Res. 1988; 9: 151-159PubMed Google Scholar, Hull R.L. J. Cnop M. Kahn S.E. Islet amyloid the pancreas and PubMed Scopus Google Scholar suggesting that the for pancreas is to have the present is and with to islet amyloid deposition and in β-cell in type 2 diabetes. are in The first is the that amyloid deposition contributes to β-cell in type 2 in with from in studies and from in A. B. Pancreatic islet of associated with diabetes PubMed Scopus Google Scholar, J. D. S. Butler P.C. The of islet amyloid polypeptide is by amyloid PubMed Scopus Google Scholar, J. K. Hull R.L. S. K. Tong J. J. Kahn S.E. Amyloid formation in of of human 52: PubMed Scopus Google Scholar, A.E. Janson J. Butler P.C. Increased beta-cell apoptosis in beta-cell mass in of type 2 for of islet amyloid formation of 2003; 52: PubMed Scopus Google Scholar, A. Oberholzer J. of amyloid polypeptide expression islet amyloid formation and of human islets in 2008; PubMed Scopus Google Scholar, S. Hull R.L. J. K. R. Kahn S.E. is by islet amyloid formation and 52: PubMed Scopus Google Scholar, M. Amyloid of human PubMed Scopus Google Scholar the may also that amyloid deposition may occur as a of the increased β-cell that occurs in or amyloid deposition may but contribute to β-cell The is that is possible from a of to whether islet amyloid deposition and/or the associated in the β-cell mass are to to impaired insulin secretion and/or have that islet amyloid deposition in human pancreatic islets is associated with decreased β-cell area and increased β-cell apoptosis. β-cell apoptosis was associated with decreased β-cell a for the of amyloid in the of β cells in type 2 diabetes and that at or islet amyloid deposition may have in β-cell mass in type 2 diabetes. We and for We for American of the a of that in and of the of The American of the was The is