Islet amyloid and islet amyloid polypeptide in cynomolgus macaques (Macaca fascicularis): An animal model of human non-insulin-dependent diabetes mellitus

T. D. O'Brien, J. D. Wagner, K. N. Litwak, C. S. Carlson, W. T. Cefalu, K. Jordan, K. H. Johnson, P. C. Butler

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

To further characterize spontaneous diabetes mellitus in cynomolgus macaques (Macaca fascicularis) as a model for human non-insulin-dependent diabetes mellitus (NIDDM), we evaluated the morphologic characteristics of the endocrine pancreas of 4 diabetic and 12 age-matched nondiabetic cynomolgus macaques. In addition, the cDNA-predicted amino acid sequence for islet amyloid polypeptide (IAPP) of this species was determined. Islet amyloid deposits exhibiting typical congophilia and green birefringence were found in 4/4 diabetic animals and in 8/12 nondiabetics. Islet amyloid deposits were significantly more extensive in the diabetic macaques (P = 0.001), in which they occupied a mean of 60% of the islet area. In contrast, in the nondiabetic group the maximum islet area occupied by amyloid was 24% (group mean = 6.8%), with four animals having no detectable islet amyloid. Amyloid deposits consistently showed immunoreactivity for LAPP but not for insulin. Comparisons between group means for diabetic versus nondiabetic macaques showed significantly greater islet area (P = 0.01, 85,390 versus 36,540 μm2) and significantly greater islet area fraction (P = 0.02, 0.065 versus 0.032) for the diabetic group. The cDNA-predicted amino acid sequence for cynomolgus IAPP was identical to that previously reported for pig-tail macaques (M. nemestrina) and had 92%, 86%, and 84% amino acid sequence identity with human, domestic cat, and murine IAPPs, respectively. These findings support the use of cynomolgus macaques as an animal model of human NIDDM.

Original languageEnglish (US)
Pages (from-to)479-485
Number of pages7
JournalVeterinary pathology
Volume33
Issue number5
DOIs
StatePublished - Sep 1996

Bibliographical note

Funding Information:
This work was supported by the following grants from the National Institutes of Health: DK 44341 (to PCB), PO2-RR08562 (to JDW, CSC, WTC), KO1-RR00072 (to JDW), and RR07009 (to KNL), and by grants from the Taylor Foundation (to KHJ, TDO).

Keywords

  • Diabetes mellitus
  • Islet amyloid
  • Islet amyloid polypeptide
  • Macaques

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