The pathophysiology of experimental insulin-deficient diabetes in the monkey. Implications for pancreatic transplantation.
In an 11-year study of experimental insulin-deficient diabetes (IDDM) induced in rhesus monkeys by streptozotocin or total pancreatectomy, the authors have found that pathophysiologic changes occur in eye and kidney, which closely resemble the early stages of human insulin deficient diabetes mellitus (IDDM). In addition, morphologic changes of thickening of glomerular capillary basement membrane and expansion of mesangial matrix (by light microscopy) appear within 3 years of onset of hyperglycemia. However, progression to irreversible complications of advanced diabetic nephropathy or proliferative retinopathy, have not occurred. This animal model resembles human disease in that the animals tend to become ketotic unless maintained with exogenous insulin; C-peptide production is low to absent, and large amounts of glycosylated hemoglobin develop within a month of onset. The monkeys differ from humans in the absence of hypertension and hyperlipidemia. The authors suggest that the abnormalities in basement membrane form and function caused by hyperglycemia form the necessary background upon which other factors, such as hypertension and hyperlipidemia, then act to cause irreversible complications. The role of pancreatic transplantation is in prevention of these background changes.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002096:C-Peptide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D003928:Diabetic Nephropathies / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000503:physiopathology; D005123:Eye / Q000473:pathology / Q000503:physiopathology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006984:Hypertrophy / Q000209:etiology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008253:Macaca mulatta; D016035:Pancreas Transplantation; D011507:Proteinuria / Q000503:physiopathology
D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin