Islet amyloid in type 2 (non-insulin-dependent) diabetes

Clark, Anne; Chargé, Sophie; Badman, Michael K.; Koning, Eelco J.P. de

doi:10.1111/j.1699-0463.1996.tb00680.x

Cited by 29 publications

(26 citation statements)

References 36 publications

(21 reference statements)

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“…Because of differences in sample size and diagnostic criteria, the prevalence of islet amyloid reported in type 2 diabetic patients varies substantially (4,5,10). For example, the widely cited study by Westermark and Wilander (31) showed that islet amyloid was found in 100% of their sample of only 12 Caucasian patients with adult onset of diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…IAPP is the building block of islet amyloid deposits (5,10,24). Although Congo red is not a specific marker for IAPP, it is as sensitive a marker for islet amyloid as IAPP immunolabeling (22).…”

Section: Methodsmentioning

confidence: 99%

“…Islet amyloid is most diffuse and abundant in type 2 diabetic patients on insulin therapy (8,9). All these findings point to an intimate association between islet amyloid and ␤-cell dysfunction in type 2 diabetes (5,10,11).…”

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confidence: 97%

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Prevalence and Clinicopathological Characteristics of Islet Amyloid in Chinese Patients With Type 2 Diabetes

et al. 2003

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Islet amyloid has been suggested to be an important link between insulin resistance and ␤-cell dysfunction in type 2 diabetes. To investigate the prevalence and clinicopathological characteristics of islet amyloid, we examined consecutive autopsies of 235 Chinese patients with type 2 diabetes and 533 nondiabetic subjects. Islet amyloid deposits were identified using Congo red staining and quantitated by image analysis. We found that 3.0% of the nondiabetic subjects versus 39.6% of the diabetic patients displayed islet amyloid (P < 0.001). In diabetic patients, the amyloid deposits occupied a mean islet area of 36.2%, which was positively associated with BMI, blood pressure, and glycemic control. Pancreatic fibrosis and fat infiltration were more frequently found in diabetic patients with islet amyloid than those without islet amyloid, whereas pancreatic arteriosclerosis was identified in all diabetic patients. These findings suggest that islet amyloid deposits reflect greater insulin resistance and islet failure in a subgroup of type 2 diabetic patients. Islet failure may also have been exacerbated by fat infiltration, fibrosis, and arteriosclerosis. Optimal blood pressure and metabolic control may reduce these pathological changes and help preserve islet cell mass. Diabetes 52: 2759 -2766, 2003

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Prevalence and Clinicopathological Characteristics of Islet Amyloid in Chinese Patients With Type 2 Diabetes

et al. 2003

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“…Some studies have found an association of this ␤-cell failure with the deposition of islet amyloid in the pancreas (3). We and others have previously reported the generation of transgenic animal models that exhibit human islet amyloid polypeptide (huIAPP)-dependent hyperglycemia associated with loss of ␤-cell mass and/or amyloid deposition (3)(4)(5). One model is described herein as the Lean-huIAPP transgenic line [FVB/N-Tg(IAPP)6Jdm/Tg(IAPP)6Jdm] (6).…”

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confidence: 94%

“…Diabetes 51:2158 -2169, 2002 T ype 2 diabetes is characterized by both impaired insulin action (1) and failure of ␤-cells to compensate with increased insulin secretion (2). Some studies have found an association of this ␤-cell failure with the deposition of islet amyloid in the pancreas (3). We and others have previously reported the generation of transgenic animal models that exhibit human islet amyloid polypeptide (huIAPP)-dependent hyperglycemia associated with loss of ␤-cell mass and/or amyloid deposition (3)(4)(5).…”

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confidence: 99%

Estrogen Can Prevent or Reverse Obesity and Diabetes in Mice Expressing Human Islet Amyloid Polypeptide

Geisler

Zawalich

et al. 2002

Diabetes

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Type 2 diabetes is characterized by loss of ␤-cell mass and concomitant deposition of amyloid derived from islet amyloid polypeptide (IAPP). Previously we have shown that expression of human IAPP (huIAPP) in islets of transgenic mice results in either a rapid onset of hyperglycemia in mice homozygous for the huIAPP transgene on a lean background (FVB/N) or a gradual hyperglycemia in mice hemizygous for the huIAPP transgene on an obese background (A vy /A). In both strains, only the males routinely develop diabetes. To investigate this sexual dimorphism, we treated young prediabetic A vy /A mice transgenic for huIAPP (huIAPP-A vy ) with 17␤-estradiol (E2). The treatment completely blocked the progression to hyperglycemia but also prevented the associated weight gain in these mice. Immunohistochemistry of pancreatic sections demonstrated normal islet morphology with no apparent deposition of islet amyloid. E2 treatment of 1-year-old huIAPP-A vy diabetic males rapidly reverses obesity and hyperglycemia. To determine the effects of E2 in a nonobese model, we also treated prediabetic, ad libitum-fed and pair-fed Lean-huIAPP transgenic males. E2 completely blocked the progression to hyperglycemia with no significant effect on body weight. Pancreatic insulin content and plasma insulin concentration of Lean-huIAPP transgenic mice increased in a dose-dependent manner. We demonstrated the presence of estrogen receptor (ER)-␣ mRNA in mouse and human islets. By also confirming the presence of ER-␣ protein in islets, we discovered a novel 58-kDa ER-␣ isoform in mice and a 52-kDa isoform in humans, in the absence of the classic 67-kDa protein found in most tissues of both species. The demonstrated presence of ER-␣ in mouse and human islets is consistent with a direct effect on islet function. We conclude that exogenous E2 administered to male mice may block human IAPP-mediated ␤-cell loss both by direct action on ␤-cells and by decreasing insulin demand through inhibition of weight gain or increasing insulin action.

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Amylin and Related Proteins: Physiology and Pathophysiology

Cooper

2001

Comprehensive Physiology

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The sections in this article are: Protein Chemistry of Amylin Isolation, Structure, Nomenclature, and Evolutionary Relationships Chemical Synthesis Molecular Structure of Soluble Amylin Amylin as the Monomer of Islet Amyloid Molecular Biology Preproamylin Structure and Chromosomal Location of the Human Amylin Gene A Disease‐Associated Mutation in Human Amylin Biosynthesis and Secretion of Amylin Measurement of Amylin Concentrations Tissue Localization and Content Regulation of Biosynthesis Amylin in Extra‐Islet Tissues Circulating Concentrations and Pancreatic Secretion Effects of Secretion Modulators Amylin Secretion in Humans The Amylin Family: Role in the Regulation of Fuel Metabolism Insulin Resistance In Vivo Actions in Skeletal Muscle Role of Calcitonin Gene‐Related Peptide in Skeletal Muscle Metabolism Actions in the Liver Adipose Tissue Regulation of Pancreatic Function Endocrine Pancreas Exocrine Pancreas Regulation of The Gastrointestinal Tract Effects on Gastric Function Intestinal Function Actions in The Central Nervous System: Modulation of Appetite Actions in The Cardiovascular System Calcitonin Gene‐Related Peptide Adrenomedullin Biological Actions of Adrenomedullin in the Cardiovascular System Vascular Actions of Amylin Renal Function Role of Amylin in the Regulation of Renal Function Adrenomedullin: Roles in Renal Function and Sodium Homeostasis Effects on Calcium Metabolism and Bone Actions of Amylin Other Biological Actions Respiratory System Effects in Endocrine Tissues Other than Pancreas Effects in the Immune System Receptors for Amylin and Related Proteins Receptor Nomenclature Pharmacological and Biochemical Studies Calcitonin Receptors Specific Calcitonin Gene‐Related Peptide Binding Sites that Can Interact with Amylin Amylin Binding to Skeletal Muscle and Liver Biochemical Characterization of Putative Amylin and Calcitonin Gene‐Related Peptide Receptors Disease Associations Insulin‐Dependent Diabetes Mellitus Animal Models of Insulin Resistance, Obesity, and Diabetes Obesity and Non‐Insulin‐Dependent Diabetes Mellitus in Humans Other Diabetic Syndromes Amylin in Endocrine Neoplasms Relationship to Aging Other Diseases Conclusion and Future Prospects

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Islet amyloid in type 2 (non-insulin-dependent) diabetes

Cited by 29 publications

References 36 publications

Prevalence and Clinicopathological Characteristics of Islet Amyloid in Chinese Patients With Type 2 Diabetes

Prevalence and Clinicopathological Characteristics of Islet Amyloid in Chinese Patients With Type 2 Diabetes

Estrogen Can Prevent or Reverse Obesity and Diabetes in Mice Expressing Human Islet Amyloid Polypeptide

Amylin and Related Proteins: Physiology and Pathophysiology

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