title: The role of islet secretory function in the development of diabetes in the GK Wistar rat.
abstract: Insulin secretion and glucose metabolism were compared in islets isolated from GK Wistar rats (a non-obese, spontaneous model of non-insulin-dependent diabetes mellitus) and control Wistars aged 8 and 14 weeks. By 8 weeks of age, GK Wistar rats were clearly diabetic as indicated by non-fasting plasma glucose concentrations and impaired glucose tolerance. Islet insulin content was not significantly different to controls at either age. In islets from 14-week-old GK Wistar rats glucose-stimulated insulin release (6-16 mmol/l glucose) was significantly reduced to 25-50% of controls in static incubations (p < 0.001). In perifusion, glucose-stimulated insulin release was reduced by 90% for first phase (p < 0.01) and by 75% for second phase (p < 0.05). The responses to arginine and 2 alpha Ketoisocaproate in islets were similar to those in controls. In contrast, islets isolated from 8-week-old GK Wistar rats exhibited no significant reduction in glucose-stimulated insulin secretion in static incubations. In perifusion, although both first and second phases of glucose-stimulated insulin release were slightly reduced, these were not significantly different to controls. Islets from 8-week-old GK Wistar rats failed however to respond to stimulation by glyceraldehyde. Raising the medium glucose concentration to 16 mmol/l significantly increased rates of glucose utilisation ([3H] H2O production from 5-[3H] glucose) and oxidation ([14C] CO2 production from U-[14C] glucose) in islets isolated from 8-week-old control and GK Wistar rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Division of Basic Medical Science, St. Mary's Hospital Medical School, Imperial College, London, UK.
authors: S J
authors: SJ
authors: Hughes
authors: K
authors: K
authors: Suzuki
authors: Y
authors: Y
authors: Goto
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005951:Glucose Tolerance Test; D005985:Glyceraldehyde / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D005985:Glyceraldehyde; D011189:Potassium Chloride; D001120:Arginine; D005947:Glucose; D005990:Glycerol