The role of islet secretory function in the development of diabetes in the GK Wistar rat.
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)
Hughes
S J
SJ
Division of Basic Medical Science, St. Mary's Hospital Medical School, Imperial College, London, UK.
Suzuki
K
K
Goto
Y
Y
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
D001786:Blood Glucose; D005985:Glyceraldehyde; D011189:Potassium Chloride; D001120:Arginine; D005947:Glucose; D005990:Glycerol