Islet neuronal abnormalities associated with impaired insulin secretion in type 2 diabetes in the Chinese hamster.
This study examined the relationship between islet neurohormonal characteristics and the defective glucose-stimulated insulin secretion in genetic type 2 diabetic Chinese hamsters. Two different sublines were studied: diabetes-prone CHIG hamsters and control CHIA hamsters. The CHIG hamsters were divided into three subgroups, depending on severity of hyperglycemia. Compared to normoglycemic CHIG hamsters and control CHIA hamsters, severely hyperglycemic CHIG hamsters (glucose > 15 mmol/l) showed marked glucose intolerance during i.p. glucose tolerance test and 75% impairment of glucose-stimulated insulin secretion from isolated islets. Mildly hyperglycemic CHIG animals (glucose 7.2-15 mmol/l) showed only moderate glucose intolerance and a 60% impairment of glucose-stimulated insulin secretion from the islets. Immunostaining for neuropeptide Y and tyrosine hydroxylase (markers for adrenergic nerves) and for vasoactive intestinal peptide (marker for cholinergic nerves) revealed significant reduction in immunostaining of islets in the severely but not in the mildly hyperglycemic animals, compared to control CHIA hamsters. The study therefore provides evidence that in this model of type 2 diabetes in Chinese hamsters, severe hyperglycemia is accompanied not only by marked glucose intolerance and islet dysfunction but also by reduced islet innervation. This suggests that islet neuronal alterations may contribute to islet dysfunction in severe but not in mild diabetes.
Kohnert
K D
KD
Department of Pathophysiology, University of Greifswald, Karlsburg, Germany.
Axcrona
U M
UM
Hehmke
B
B
Klöting
I
I
Sundler
F
F
Ahrén
B
B
D000818:Animals; D017849:Animals, Inbred Strains; D001786:Blood Glucose / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000503:physiopathology; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009412:Nerve Fibers / Q000737:chemistry / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism; D010179:Pancreas / Q000294:innervation / Q000503:physiopathology; D010187:Pancreatic Hormones / Q000378:metabolism; D019894:Peptide YY / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D009479:Neuropeptides; D010187:Pancreatic Hormones; D019894:Peptide YY; D005947:Glucose