Diabetes mellitus: relationships of nonhuman primates and other animal models to human forms of diabetes.

Results from studies with M. nigra allow some conclusions and predictions about the etiology and development of diabetes relative to the islet lesion in monkeys and human beings. Some factor or factors must initiate the lesion; whether this is genetic, environmental, or a combination of both is not known. Amyloid is not the initiating factor to the islet lesion, but appears later as there is deterioration of cells. Sufficient evidence does not yet exist to choose from among the alternatives regarding the source of amyloid. With gradual deterioration of cells and replacement by amyloid, secretion of insulin is impaired and concentrations of glucagon increase. Sufficient circulating insulin is probably chronically available to the cells in this moderately impaired state, so that an acute decrease in delta IRI in response to glucose in an iv-administered GTT does not cause significant impairment in glucose clearance. The increase in circulating glucagon is probably due to a loss of controls on alpha-cell secretion or synthesis of glucagon. Fasting glucose levels increase but remain within the nondiabetic range. Eventually there is sufficient accretion of amyloid, usually greater than 50%, so that substantial beta-cell loss occurs and the monkey can no longer maintain fasting normoglycemia. The monkey then is hyperglycemic and hypoinsulinemic. Only at this time are the impairments detectable by the usual diagnostic clinical criterion of hyperglycemia. The ICAs arise in response to secretory cell deterioration and are present until there no longer are sufficient cells to elicit an immune response. Results from M. nigra can give insight into a similar condition that probably exists in a subpopulation of older diabetic humans. Humans probably pass through stages similar to those discerned in monkeys. Nondiabetic humans with sufficient beta cells to sustain adequate secretion of insulin, but with moderate amyloid infiltration, probably would be in a category equivalent to BD monkeys; since these people are not overtly hyperglycemic, they are not clinically recognizable as diabetic and would be classified retrospectively as nondiabetic. Continued loss of cells with concomitant amyloid deposition would eventually lead to hyperglycemia; if examined at autopsy, these people would have visible islet amyloid as well as a retrospective diagnosis of diabetes. Older type II diabetic humans with ICA usually proceed to insulin therapy more rapidly than do those who are ICA negative (Irvine et al., 1977; Del Prete et al., 1977; Gray et al., 1980).(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of quantity and unsaturation of dietary fat on serum components in normal and diabetic Macaca nigra.

Dietary fat affects serum lipids independently of dietary cholesterol. Normal and diabetic monkeys (Macaca nigra) were fed cereal-based, specially formulated diets with either a low fat (LF = 2.5%) or a higher fat (13.2%) content; the latter had varying concentrations of safflower and coconut oil to attain greater polyunsaturation (SFO) or saturation (CCO) in the diets. Dietary cholesterol was less than 0.01%. Serum triglyceride concentrations were greatest when monkeys consumed the LF (higher carbohydrate) diet and lowest when they consumed the SFO diet. Concentrations were greater in diabetic than in normal monkeys fed the LF and SFO diets, but both groups had similar concentrations when fed the CCO diet. Cholesterol levels in diabetic monkeys were only slightly higher than in normals regardless of diet; in both groups, levels were lowest when the LF diet was fed and highest when the CCO diet was fed. The quantity of fat had a greater effect on serum cholesterol than did the degree of polyunsaturation. In both groups, triglyceride concentrations correlated significantly with VLDL protein, and cholesterol levels correlated with LDL protein. Thus the responses of Macaca nigra to dietary fat manipulation depend upon both the diet fat content and composition as well as the normal or diabetic metabolic state of each monkey.