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Delayed Ca2+ response to glucose in diabetic GK rat
S Zaitsev1, I Efanova, C G Ostenson
1Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Biochemical and Biophysical Research Communications
|November 5, 1997
Summary
The Goto-Kakizaki rat, a model for type 2 diabetes, shows delayed calcium responses in pancreatic islets due to impaired glucose metabolism. This affects insulin secretion, highlighting a key defect in diabetic islet function.
Area of Science:
- Endocrinology
- Metabolic Research
- Cell Physiology
Background:
- The Goto-Kakizaki (GK) rat is a valuable model for non-insulin dependent diabetes mellitus (NIDDM) due to its hyperglycemia and impaired insulin secretion.
- Cytosolic free calcium concentration ([Ca2+]i) is a critical regulator of insulin secretion from pancreatic beta-cells.
Purpose of the Study:
- To investigate the handling of cytosolic free Ca2+ concentration ([Ca2+]i) in pancreatic islets of the GK rat model of NIDDM.
- To compare the [Ca2+]i response to glucose and arginine stimulation in GK rat islets versus control Wistar rat islets.
Main Methods:
- Isolation of single pancreatic islets from GK and Wistar rats.
- Measurement of cytosolic free Ca2+ concentration ([Ca2+]i) using fluorescence indicators.
- Stimulation of islets with high glucose (16.7 mM) and arginine (20 mM).
Main Results:
- Glucose stimulation induced a delayed [Ca2+]i response in GK rat pancreatic islets compared to Wistar rat islets.
- Arginine stimulation (not detailed in abstract, but implied as a control) may show differential effects.
- The delay in [Ca2+]i response in GK islets is linked to impaired glucose metabolism.
Conclusions:
- Defective glucose metabolism in GK rat pancreatic islets leads to a delayed cytosolic Ca2+ influx.
- This impaired calcium handling is a significant factor contributing to the poor glucose-induced insulin secretion observed in NIDDM models.
- Understanding these cellular defects is crucial for developing targeted therapies for type 2 diabetes.