Histochemical changes in pancreatic islets obtained from obese Zucker rats (fa/fa) on a diabetogenic diet. No evidence for non-enzymatic protein glycation in endocrine cells.
Genetically obese Zucker rats (fa/fa) on a diabetogenic diet rich in lard and sucrose develop chronic hyperglycemia accompanied by severe hyperinsulinemia. Non-enzymatically glycated protein content was increased in tendon (p < 0.0001) and aorta (p < 0.04), but not nerve, from hyperglycemic rats as compared to normoglycemic lean litter-mates on a conventional chow diet (mmol furosine/mol tyrosine in tissue hydrolysate from 61-week-old rats: tendon, 29.8 +/- 1.8 vs 25.9 +/- 1.3; aorta, 12.0 +/- 1.0 vs 11.0 +/- 1.1). In pancreatic islets, non-enzymatically glycated protein was neither found in lean rats of any age nor in the obese up to an age of 36 weeks. At an age of 61 weeks, non-enzymatically glycated protein accumulated in islets of obese animals, resulting in levels of 17.02-44.65 mmol furosine/mol tyrosine. This rise in islet glycated protein content was not accompanied by a comparable increase in plasma glycemia, but simultaneous histological examination of pancreatic tissue revealed fibrosis of islets. Fibers were probably of collagenic quality without islet amyloid polypeptide immunoreactivity. Because collagen is known to be highly susceptible to non-enzymatic glycation, we suspect that collagenic fibers but not endocrine cells are the main source of glycated protein accumulation in these islets. Hence, our data do not give evidence that non-enzymatic protein glycation plays a role in the islet degeneration occurring in hyperglycemia. Furthermore, immunohistochemical staining for various endocrine peptides did not suggest loss of any hormone-producing cell type or defective pancreatic hormone production in hyperglycemic old, obese Zucker rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Fürnsinn
C
C
Department of Medicine III, University of Vienna, Austria.
Komjati
M
M
Madsen
O D
OD
Schneider
B
B
Waldhäusl
W
W
D000818:Animals; D001011:Aorta / Q000378:metabolism; D004032:Diet; D006651:Histocytochemistry; D006943:Hyperglycemia / Q000378:metabolism; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D012584:Sciatic Nerve / Q000378:metabolism; D013194:Staining and Labeling; D013710:Tendons / Q000378:metabolism
D011506:Proteins