The role of islet secretory function in the development of diabetes in the GK Wistar rat

Diabetologia. 1994 Sep;37(9):863-70. doi: 10.1007/BF00400940.


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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Arginine / pharmacology
  • Blood Glucose / metabolism*
  • Body Weight
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Glucose / metabolism
  • Glucose / pharmacology
  • Glucose Tolerance Test
  • Glyceraldehyde / pharmacology
  • Glycerol / metabolism
  • In Vitro Techniques
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / growth & development
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Male
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Wistar
  • Reference Values


  • Blood Glucose
  • Glyceraldehyde
  • Potassium Chloride
  • Arginine
  • Glucose
  • Glycerol