Diabetes & Metabolism Journal

Original Article

The Role of cAMP/PKA Activation on Exendin-4-Induced Cyclin D1 Expression in INS-1 Cell.: Gyeong Ryul Ryu, Jung Hoon Kang, Hwa In Jang, Seung Hyun Ko, In Kyung Jeong, Duck Joo Rhie, Shin Hee Yoon, Sang June Hahn, Yang Hyeok Jo, Myung Suk Kim, Myung Jun Kim; Korean Diabetes J. 2005;29(4):295-303. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Glucagon-like peptide-1(GLP-1) and exendin-4(EX-4) have been known to induce pancreatic islet proliferation and increases in the betacell mass. Cyclin D1 is a key protein responsible for the entry of the G into the S phase, thereby contributing to cell proliferation. Therefore, the effect of EX-4 on the expression of cyclin D1 in INS-1 cells, a rat pancreatic betacell line, was investigated. The involvement of either mitogen-activated protein kinases(MAPKs) or cyclic adenosine 5'-monophosphate/protein kinase A(cAMP/ PKA) in the EX-4-induced cyclin D1 expression was also examined. METHODS: INS-1 cells were treated with EX-4 (10 nM), and the cyclin D1 protein levels then determined by Western blot. To investigate the involvement of MAPKs in the EX-4- induced cyclin D1 expression, either a combined treatment of MAPKs inhibitors or transient transfection of extracellular signal-regulated kinase-1 (ERK1) was performed. The effect of cAMP on the EX-4-induced cyclin D1 expression was also examined by treatments with forskolin, an adenylyl cyclase activator, and H-89, a PKA inhibitor. RESULTS: EX-4 increased the expression of cyclin D1 protein in a dose-dependent manner. Although EX-4 induced phosphorylation of ERK1/2, the treatment with PD 98059 or the overexpression of ERK1 had no effect on the EX-4-induced cyclin D1 expression. However, forskolin significantly induced the expression of cyclin D1, whereas the pretreatment of H-89 inhibited the EX-4-induced cyclin D1 expression. CONCLUSION: These results suggest that EX-4 induce cyclin D1 expression in INS-1 cells via cAMP/PKA pathway, but this is not due to ERK activation.

Case Report

A Case of Diabetic Hyporeninemic Hypoaldosteronism Associated with Muscular Symptoms Due to Hyperkalemia.: Jee Young Oh, Yeon Ah Sung, Sang Woon Lee, Joon Sim; Korean Diabetes J. 1998;22(4):568-573. Published online January 1, 2001

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Abstract PDF: Diabetic hyporeninemic hypoaldosteronism is clinically defined syndrome which is characterized by hyperkalemic hyperchloremic metabolic acidosis in patients with diabetic autonomic neuropathy and nephropathy. The major cause of hyporeninemia in diabetes mellitus is the impairement of activation from glycated prorenin to renin. Hyperkalemia is major disorder of this syndrome which is almostly chroniclly developed but acutely developed in case of diabetic patients because of hyperglycemia and hyperkalemic symptoms are usually absent or mild. We experienced a case of diabetic hyporeninemic hypoaldosteronis complicated with acute severe hyperkalemia, myalgia and muscle weakness. The patient complained severe pain and muscle weakness of posterior neck and both lower extremities, serum potassium concentration was 8.5 mEq/L, serum muscle enzymes were very high and electrocardio gram showed ventricular premature beat and generalized T wave inversion. Plasma renin activity and aldosterone concen trations were below normal limits and not stimulated by furosemide administration. After the conservative management of hyperkalemia and g]ycemic control with insulin, serum potassium leve1 and muscle enzymes were normalized.

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