Alterations in basal and glucose-stimulated voltage-dependent Ca2+ channel activities in pancreatic beta cells of non-insulin-dependent diabetes mellitus GK rats

J Clin Invest. 1996 Jun 1;97(11):2417-25. doi: 10.1172/JCI118688.


In genetically occurring non-insulin-dependent diabetes mellitus (NIDDM) model rats (GK rats), the activities of L- and T-type Ca2+ channels in pancreatic beta cells are found to be augmented, by measuring the Ba2+ currents via these channels using whole-cell patch-clamp technique, while the patterns of the current-voltage curves are indistinguishable. The hyper-responsiveness of insulin secretion to nonglucose depolarizing stimuli observed in NIDDM beta cells could be the result, therefore, of increased voltage-dependent Ca2+ channel activity. Perforated patch-clamp recordings reveal that the augmentation of L-type Ca2+ channel activity by glucose is markedly less pronounced in GK beta cells than in control beta cells, while glucose-induced augmentation of T-type Ca2+ channel activity is observed neither in the control nor in the GK beta cells. This lack of glucose-induced augmentation of L-type Ca2+ channel activity in GK beta cells might be causatively related to the selective impairment of glucose-induced insulin secretion in NIDDM beta cells, in conjunction with an insufficient plasma membrane depolarization due to impaired closure of the ATP-sensitive K+ channels caused by the disturbed intracellular glucose metabolism in NIDDM beta cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Calcium Channels, L-Type
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Glucose / pharmacology*
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / pathology
  • Islets of Langerhans / physiopathology*
  • Male
  • Membrane Potentials / drug effects
  • Models, Biological
  • Nitrendipine / metabolism
  • Patch-Clamp Techniques
  • Potassium / pharmacology
  • Rats
  • Rats, Mutant Strains
  • Rats, Wistar
  • Reference Values


  • Calcium Channels
  • Calcium Channels, L-Type
  • Insulin
  • Nitrendipine
  • Glucose
  • Potassium
  • Calcium