scholarly journals Intracellular amyloid-like deposits contain unprocessed pro-islet amyloid polypeptide (proIAPP) in beta cells of transgenic mice overexpressing the gene for human IAPP and transplanted human islets

Diabetologia ◽  
2006 ◽  
Vol 49 (6) ◽  
pp. 1237-1246 ◽  
Author(s):  
J. F. Paulsson ◽  
A. Andersson ◽  
P. Westermark ◽  
G. T. Westermark
Keyword(s):  
Transgenic Mice ◽  
Beta Cells ◽  
Islet Amyloid Polypeptide ◽  
Human Islets ◽  
Islet Amyloid

Differences in amyloid deposition in islets of transgenic mice expressing human islet amyloid polypeptide versus human islets implanted into nude mice

Metabolism ◽  
1999 ◽  
Vol 48 (4) ◽  
pp. 448-454 ◽  
Author(s):  
Gunilla Westermark ◽  
Per Westermark ◽  
Decio L. Eizirik ◽  
Claes Hellerström ◽  
Niles Fox ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Nude Mice ◽  
Islet Amyloid Polypeptide ◽  
Human Islets ◽  
Amyloid Deposition ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

scholarly journals Beta-cell selective KATP-channel activation protects beta-cells and human islets from human islet amyloid polypeptide induced toxicity

2010 ◽  
Vol 165 (2-3) ◽  
pp. 158-162 ◽  
Author(s):  
Robert A. Ritzel ◽  
Sajith Jayasinghe ◽  
John B. Hansen ◽  
Jeppe Sturis ◽  
Ralf Langen ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Katp Channel ◽  
Islet Amyloid Polypeptide ◽  
Human Islets ◽  
Human Islet ◽  
Islet Amyloid ◽  
Channel Activation ◽  
Human Islet Amyloid Polypeptide

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

1995 ◽  
Vol 132 (4) ◽  
pp. 487-496 ◽  
Author(s):  
Kazuo Yagui ◽  
Takahide Yamaguchi ◽  
Azuma Kanatsuka ◽  
Fumio Shimada ◽  
Choug I Huang ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transgenic Mice ◽  
Beta Cells ◽  
Amyloid Fibrils ◽  
Secretory Granules ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Amyloid Deposits

Yagui K, Yamaguchi T, Kanatsuka A, Shimada F, Huang CI, Tokuyama Y, Ohsawa H, Yamamura K, Miyazaki J. Mikata A, Yoshida S, Makino H. Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin. Eur J Endocrinol 1995:132:487–96. ISSN 0804–4643 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. Azuma Kanatsuka, Second Department of Internal Medicine, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan

Human islet amyloid polypeptide accumulates at similar sites in islets of transgenic mice and humans

Diabetes ◽  
1994 ◽  
Vol 43 (5) ◽  
pp. 640-644 ◽  
Author(s):  
E. J. de Koning ◽  
J. W. Hoppener ◽  
J. S. Verbeek ◽  
C. Oosterwijk ◽  
K. L. van Hulst ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells

Diabetes ◽  
1990 ◽  
Vol 39 (5) ◽  
pp. 634-638 ◽  
Author(s):  
S. E. Kahn ◽  
D. A. D'Alessio ◽  
M. W. Schwartz ◽  
W. Y. Fujimoto ◽  
J. W. Ensinck ◽  
...  
Keyword(s):  
Beta Cells ◽  
Islet Amyloid Polypeptide ◽  
Islet Amyloid

Strong Promoter Activity of Human and Rat Islet Amyloid Polypeptide / Amylin Gene Constructs in Mouse Beta Cells (βTC 3)

1993 ◽  
Vol 192 (2) ◽  
pp. 840-848 ◽  
Author(s):  
L. Dewit ◽  
A.D.M. Vanmansfeld ◽  
H.A.A.M. Vanteeffelen ◽  
C.J.M. Lips ◽  
J.W.M. Hoppener
Keyword(s):  
Beta Cells ◽  
Promoter Activity ◽  
Islet Amyloid Polypeptide ◽  
Islet Amyloid ◽  
Strong Promoter ◽  
Amylin Gene

scholarly journals Tetracycline Treatment Retards the Onset and Slows the Progression of Diabetes in Human Amylin/Islet Amyloid Polypeptide Transgenic Mice

Diabetes ◽  
2009 ◽  
Vol 59 (1) ◽  
pp. 161-171 ◽  
Author(s):  
J. F. Aitken ◽  
K. M. Loomes ◽  
D. W. Scott ◽  
S. Reddy ◽  
A. R.J. Phillips ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Islet Amyloid Polypeptide ◽  
Islet Amyloid ◽  
Tetracycline Treatment ◽  
Human Amylin

scholarly journals Loss of perlecan heparan sulfate glycosaminoglycans lowers body weight and decreases islet amyloid deposition in human islet amyloid polypeptide transgenic mice

2019 ◽  
Vol 32 (2) ◽  
pp. 95-102
Author(s):  
Andrew T Templin ◽  
Mahnaz Mellati ◽  
Raija Soininen ◽  
Meghan F Hogan ◽  
Nathalie Esser ◽  
...  
Keyword(s):  
Body Weight ◽  
Transgenic Mice ◽  
Heparan Sulfate ◽  
Islet Amyloid Polypeptide ◽  
Amyloid Deposition ◽  
Secretory Product ◽  
Cell Area ◽  
Β Cell ◽  
Islet Amyloid

Abstract Islet amyloid is a pathologic feature of type 2 diabetes (T2D) that is associated with β-cell loss and dysfunction. These amyloid deposits form via aggregation of the β-cell secretory product islet amyloid polypeptide (IAPP) and contain other molecules including the heparan sulfate proteoglycan perlecan. Perlecan has been shown to bind amyloidogenic human IAPP (hIAPP) via its heparan sulfate glycosaminoglycan (HS GAG) chains and to enhance hIAPP aggregation in vitro. We postulated that reducing the HS GAG content of perlecan would also decrease islet amyloid deposition in vivo. hIAPP transgenic mice were crossed with Hspg2Δ3/Δ3 mice harboring a perlecan mutation that prevents HS GAG attachment (hIAPP;Hspg2Δ3/Δ3), and male offspring from this cross were fed a high fat diet for 12 months to induce islet amyloid deposition. At the end of the study body weight, islet amyloid area, β-cell area, glucose tolerance and insulin secretion were analyzed. hIAPP;Hspg2Δ3/Δ3 mice exhibited significantly less islet amyloid deposition and greater β-cell area compared to hIAPP mice expressing wild type perlecan. hIAPP;Hspg2Δ3/Δ3 mice also gained significantly less weight than other genotypes. When adjusted for differences in body weight using multiple linear regression modeling, we found no differences in islet amyloid deposition or β-cell area between hIAPP transgenic and hIAPP;Hspg2Δ3/Δ3 mice. We conclude that loss of perlecan exon 3 reduces islet amyloid deposition in vivo through indirect effects on body weight and possibly also through direct effects on hIAPP aggregation. Both of these mechanisms may promote maintenance of glucose homeostasis in the setting of T2D.

Sign in / Sign up

Export Citation Format

Share Document