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MIN6 Cells (min6 + cell)
Selected AbstractsRab11 and its effector Rip11 participate in regulation of insulin granule exocytosisGENES TO CELLS, Issue 4 2009Kenji Sugawara Rab GTPases and their effectors play important roles in membrane trafficking between cellular compartments in eukaryotic cells. In the present study, we examined the roles of Rab11B and its effectors in insulin secretion in pancreatic ,-cells. In the mouse insulin-secreting cell line MIN6, Rab11 was co-localized with insulin-containing granules, and over-expression of the GTP- or the GDP-bound form of Rab11B significantly inhibited regulated secretion, indicating involvement of Rab11B in regulated insulin secretion. To determine the downstream signal of Rab11-mediated insulin secretion, we examined the effects of various Rab11-interacting proteins on insulin secretion, and found that Rip11 is involved in cAMP-potentiated insulin secretion but not in glucose-induced insulin secretion. Analyses by immunocytochemistry and subcellular fractionation revealed Rip11 to be co-localized with insulin granules. The inhibitory effect of the Rip11 mutant was not altered in MIN6 cells lacking Epac2, which mediates protein kinase A (PKA)-independent potentiation of insulin secretion, compared with wild-type MIN6 cells. In addition, Rip11 was found to be phosphorylated by PKA in MIN6 cells. The present study shows that both Rab11 and its effector Rip11 participate in insulin granule exocytosis and that Rip11, as a substrate of PKA, regulates the potentiation of exocytosis by cAMP in pancreatic ,-cells. [source] Analysis of a non-functional HNF-1, (TCF1) mutation in Japanese subjects with familial type 1 diabetesHUMAN MUTATION, Issue 4 2001Issei Yoshiuchi Abstract Mutations in the transcription factor hepatocyte nuclear factor-1, (HNF-1,; gene symbol TCF1) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic ,-cell dysfunction. Recent genetic studies, however, also found mutations in patients diagnosed with idiopathic (non-autoimmune based) type 1 diabetes. We identified a novel frameshift mutation (142delG) in the TCF1 gene in a family with a strong family history of type 1 diabetes and examined the functional properties of the mutant HNF 1,. The expression of the mutant protein was not detected in COS-7 cells by Western blot analysis after transfection of the mutant cDNA. This is the first case of an unstable mutant HNF-1, protein. Reporter gene analysis indicated that the mutant HNF-1, had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF-1, may lead to severe forms of diabetes like type 1 diabetes. Hum Mutat 18:345,351, 2001. © 2001 Wiley-Liss, Inc. [source] Antidiabetic activity of Croton klozchianus in rats and direct stimulation of insulin secretion in-vitroJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2008R. Govindarajan Croton klozchianus is a relatively uninvestigated species with no pharmacological or phytochemical reports available, although it has been used clinically by Ayurvedic physicians to treat diabetes. We have investigated this use by studying the insulin secretion and antidiabetic activity of C. klozchianus. Treatment of diabetic rats with aerial parts of C. klozchianus extract (CK, 100 and 300 mg kg,1 body weight) for three weeks showed significant reduction in blood glucose (45.8% after 14 days for 300 mg kg,1). C. klozchianus extract caused a significant concentration-dependent increase in insulin secretion (8-fold at 2 mg mL,1 for cells challenged with 20 mm glucose) from MIN6 cells grown as monolayers and as pseudoislets, indicating that the antidiabetic activity may have been as a result of increased insulin secretion. It also had a role on the lipid profile of the rats by causing reduction in cholesterol and triglycerides and increasing high density lipoprotein significantly. The results obtained gave some scientific support to the traditional use of the plant as a treatment for diabetes. [source] | ||||||||||