Islet amyliod polypeptide-derived amyloid deposition increases along with the duration of type 2 diabetes mellitus

Ohsawa, Haruhiko; Kanatsuka, Azuma; Mizuno, Yoshiatsu; Tokuyama, Yoshiharu; Takada, Kazushi; Mikata, Atsuo; Makino, Hideichi; Yoshida, Sho

doi:10.1016/0168-8227(92)90062-v

Cited by 19 publications

(13 citation statements)

References 15 publications

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“…These islet amyloid deposits interfere with the function of pancreatic beta cells. This thesis is compatible with the findings that IAPP-derived amyloid deposition increases along with the duration of NIDDM (38) and that the number of insulin-producing cells decreases in pancreatic islets with amyloid deposits (37). Longitudinal studies on the development of diabetes in individual Macaca nigra demonstrated that there was a gradual loss of insulinproducing cells and concurrent amyloid deposition (2).…”

Section: Resultssupporting

confidence: 88%

“…Another reason may be that, because most cases examined at autopsy are in the advanced stage of the disease, early lesions such as intracellular amyloidogenesis will not be evident but extracellular amyloid deposits will be. As IAPP immunoreactivity in beta cells of islets with amyloid deposits is diminished in human NIDDM (37,38), IAPP synthesis and contents may be decreased at this stage and thus intracellular amyloid fibril formation will not occur. Islet amyloid deposits were not observed in any of our transgenic mice examined at the age of 6 months.…”

Section: Resultsmentioning

confidence: 95%

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Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin

Yagui

Yamaguchi

Kanatsuka

et al. 1995

European Journal of Endocrinology

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To investigate the relationship between human islet amyloid polypeptide (IAPP)/amylin expression and islet amyloid deposits in the pathogenesis of human non-insulin-dependent diabetes mellitus (NIDDM), we developed transgenic mice using a human IAPP cDNA connected to an insulin promoter. Ribonucleic acid blotting and immunohistochemistry revealed the expression of the transgene in the pancreatic beta cells. Immunogold electron microscopy showed that beta-secretory granules contained the human C-terminal flanking peptide of the IAPP precursor. Reverse-phase HPLC demonstrated human and mouse IAPP amide in the pancreas. Electron microscopy showed the accumulation of fibril-like material in a considerable number of beta-secretory granules. These results suggest that in transgenic mice, the human IAPP precursor is expressed in beta cells and becomes normally sorted into beta-secretory granules in which normal conversion to mature human IAPP takes place. The human IAPP molecules, because of their amyloidogenesis, aggregate into amyloid fibrils in secretory granules. Glucose tolerance was normal at 7 months old and islet amyloid was not observed. A longer time may be required for islet amyloid deposits and hyperglycemia to develop in mice. Our working hypothesis is that in human NIDDM, IAPP aggregates into amyloid fibrils in beta-secretory granules, and that the fibrils are released into the extracellular space and islet amyloid deposits become substantial with time.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 95%

Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin

Yagui

Yamaguchi

Kanatsuka

et al. 1995

European Journal of Endocrinology

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“…IAPP deposits often co-localize with cellular degeneration [5,6], and are therefore strongly associated with the progressive loss of pancreatic β-cell mass, a hallmark of type 2 diabetes mellitus [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Islet amyloid polypeptide acts on glucose‐ stimulated beta cells to reduce voltage‐gated calcium channel activation, intracellular Ca²⁺ concentration, and insulin secretion

Zhu

Wang

et al. 2010

Diabetes Metabolism Res

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“…An increase in islet amyloid deposits has been reported in Japanese type 2 diabetic patients with long disease duration and obesity (17). However, other autopsy studies have shown that islet amyloid developed independent of duration of diabetes over 2-40 years (11,18).…”

mentioning

confidence: 98%

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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Islet amyliod polypeptide-derived amyloid deposition increases along with the duration of type 2 diabetes mellitus

Cited by 19 publications

References 15 publications

Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin

Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin

Islet amyloid polypeptide acts on glucose‐ stimulated beta cells to reduce voltage‐gated calcium channel activation, intracellular Ca²⁺ concentration, and insulin secretion

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

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Islet amyliod polypeptide-derived amyloid deposition increases along with the duration of type 2 diabetes mellitus

Cited by 19 publications

References 15 publications

Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin

Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin

Islet amyloid polypeptide acts on glucose‐ stimulated beta cells to reduce voltage‐gated calcium channel activation, intracellular Ca2+ concentration, and insulin secretion

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

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Islet amyloid polypeptide acts on glucose‐ stimulated beta cells to reduce voltage‐gated calcium channel activation, intracellular Ca²⁺ concentration, and insulin secretion