DIABETES-MELLITUS IN MACACA-MULATTA MONKEYS IS CHARACTERIZED BY ISLETAMYLOIDOSIS AND REDUCTION IN BETA-CELL POPULATION

Diabetes mellitus in Macaca mulatta rhesus monkeys is preceded by phas es of obesity and hyperinsulinaemia and is similar to Type 2 (non-insu lin-dependent) diabetes mellitus in man. To relate the progression of the disease to quantitative changes in islet morphology, post-mortem p ancreatic tissue from 26 monkeys was examined. Four groups of animals were studied: group I - young, lean and normal (n = 3); group II - old er ( > 10 years), lean and obese, normoglycaemic n = 9); group III - n ormoglycaemic and hyperinsulinaemic n = 6); group IV - diabetic (n = 8 ). Areas of islet amyloid, beta cells and islets were measured on stai ned histological sections. Islet size was larger in animals from group s III (p < 0.01) and IV (p < 0.0001) compared to groups I and II. The mean beta-cell area per islet in mum2 was increased in group III (p < 0.05) and reduced in group IV (p < 0.001) compared to groups I and II. Mean beta-cell area per islet correlated with fasting plasma insulin (r = 0.76, p < 0.001) suggesting that hyper- and hypoinsulinaemia are related to the beta-cell population. Amyloid was absent in group I but small deposits were present in three of nine (group II) and in four o f six (group III) animals, occupying between 0.03-45 % of the islet sp ace. Amyloid was present in eight of eight diabetic animals (group IV) occupying between 37-81 % of the islet area. Every islet was affected in seven of eight diabetic monkeys. There was no correlation of degre e of amyloidosis with age, body weight, body fat proportion or fasting insulin. Islet amyloid appears to precede the development of overt di abetes in Macaca mulatta and is likely to be a factor in the destructi on of islet cells and onset of hyperglycaemia.