| First Author | Leiss V | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 1 | Pages | 148-56 |
| PubMed ID | 20978093 | Mgi Jnum | J:170155 |
| Mgi Id | MGI:4944090 | Doi | 10.2337/db10-0595 |
| Citation | Leiss V, et al. (2011) Cyclic GMP kinase I modulates glucagon release from pancreatic alpha-cells. Diabetes 60(1):148-56 |
| abstractText | OBJECTIVE: The physiologic significance of the nitric oxide (NO)/cGMP signaling pathway in islets is unclear. We hypothesized that cGMP-dependent protein kinase type I (cGKI) is directly involved in the secretion of islet hormones and glucose homeostasis. RESEARCH DESIGN AND METHODS: Gene-targeted mice that lack cGKI in islets (conventional cGKI mutants and cGKIalpha and Ibeta rescue mice [alpha/betaRM] that express cGKI only in smooth muscle) were studied in comparison to control (CTR) mice. cGKI expression was mapped in the endocrine pancreas by Western blot, immuno-histochemistry, and islet-specific recombination analysis. Insulin, glucagon secretion, and cytosolic Ca(2)(+) ([Ca(2)(+)](i)) were assayed by radioimmunoassay and FURA-2 measurements, respectively. Serum levels of islet hormones were analyzed at fasting and upon glucose challenge (2 g/kg) in vivo. RESULTS: Immunohistochemistry showed that cGKI is present in alpha- but not in beta-cells in islets of Langerhans. Mice that lack alpha-cell cGKI had significantly elevated fasting glucose and glucagon levels, whereas serum insulin levels were unchanged. High glucose concentrations strongly suppressed the glucagon release in CTR mice, but had only a moderate effect on islets that lacked cGKI. 8-Br-cGMP reduced stimulated [Ca(2)(+)](i) levels and glucagon release rates of CTR islets at 0.5 mmol/l glucose, but was without effect on [Ca(2)(+)](i) or hormone release in cGKI-deficient islets. CONCLUSIONS: We propose that cGKI modulates glucagon release by suppression of [Ca(2)(+)](i) in alpha-cells. |
