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)
D000818:Animals; D001323:Autoantibodies; D003920:Diabetes Mellitus / Q000503:physiopathology / Q000662:veterinary; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004777:Environment; D005819:Genetic Markers; D006680:HLA Antigens; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D009765:Obesity; D011323:Primates; D012377:Rodentia
D001323:Autoantibodies; D005819:Genetic Markers; D006680:HLA Antigens