scholarly journals Activation of the AMP-activated protein kinase enhances glucose-stimulated insulin secretion in mouse β-cells

Islets ◽  
2010 ◽  
Vol 2 (3) ◽  
pp. 156-163 ◽  
Author(s):  
Martina Düfer ◽  
Katja Noack ◽  
Peter Krippeit-Drews ◽  
Gisela Drews
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Β Cells ◽  
Glucose Stimulated Insulin Secretion ◽  
Amp Activated Protein Kinase

scholarly journals Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression

2003 ◽  
Vol 371 (3) ◽  
pp. 761-774 ◽  
Author(s):  
Gabriela da SILVA XAVIER ◽  
Isabelle LECLERC ◽  
Aniko VARADI ◽  
Takashi TSUBOI ◽  
S. Kelly MOULE ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Active Form ◽  
Dominant Negative ◽  
Β Cells ◽  
Dominant Negative Form ◽  
Ampk Activity ◽  
Glucose Stimulated Insulin Secretion ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) has recently been implicated in the control of preproinsulin gene expression in pancreatic islet β-cells [da Silva Xavier, Leclerc, Salt, Doiron, Hardie, Kahn and Rutter (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 4023–4028]. Using pharmacological and molecular strategies to regulate AMPK activity in rat islets and clonal MIN6 β-cells, we show here that the effects of AMPK are exerted largely upstream of insulin release. Thus forced increases in AMPK activity achieved pharmacologically with 5-amino-4-imidazolecarboxamide riboside (AICAR), or by adenoviral overexpression of a truncated, constitutively active form of the enzyme (AMPKα1.T172D), blocked glucose-stimulated insulin secretion. In MIN6 cells, activation of AMPK suppressed glucose metabolism, as assessed by changes in total, cytosolic or mitochondrial [ATP] and NAD(P)H, and reduced increases in intracellular [Ca2+] caused by either glucose or tolbutamide. By contrast, inactivation of AMPK by expression of a dominant-negative form of the enzyme mutated in the catalytic site (AMPKα1.D157A) did not affect glucose-stimulated increases in [ATP], NAD(P)H or intracellular [Ca2+], but led to the unregulated release of insulin. These results indicate that inhibition of AMPK by glucose is essential for the activation of insulin secretion by the sugar, and may contribute to the transcriptional stimulation of the preproinsulin gene. Modulation of AMPK activity in the β-cell may thus represent a novel therapeutic strategy for the treatment of type 2 diabetes mellitus.

scholarly journals AMP-activated protein kinase as regulator of P2Y6 receptor-induced insulin secretion in mouse pancreatic β-cells

2013 ◽  
Vol 85 (7) ◽  
pp. 991-998 ◽  
Author(s):  
Ramachandran Balasubramanian ◽  
Hiroshi Maruoka ◽  
P. Suresh Jayasekara ◽  
Zhan-Guo Gao ◽  
Kenneth A. Jacobson
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
P2y6 Receptor ◽  
Amp Activated Protein Kinase

scholarly journals Decreased Insulin Secretion and Accumulation of Triglyceride in β Cells Overexpressing a Dominant-negative Form of AMP-activated Protein Kinase

2010 ◽  
Vol 57 (2) ◽  
pp. 141-152 ◽  
Author(s):  
Yukiko OKAZAKI ◽  
Kazuhiro ETO ◽  
Tokuyuki YAMASHITA ◽  
Masayuki OKAMOTO ◽  
Mitsuru OHSUGI ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Dominant Negative ◽  
Β Cells ◽  
Dominant Negative Form ◽  
Amp Activated Protein Kinase ◽  
Negative Form

Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion

2004 ◽  
Vol 286 (6) ◽  
pp. E1023-E1031 ◽  
Author(s):  
Isabelle Leclerc ◽  
Wolfram W. Woltersdorf ◽  
Gabriela da Silva Xavier ◽  
Rebecca L. Rowe ◽  
Sarah E. Cross ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Pancreatic Islets ◽  
Human Islets ◽  
Β Cells ◽  
Min6 Cells ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

Metformin, a drug widely used in the treatment of type 2 diabetes, has recently been shown to act on skeletal muscle and liver in part through the activation of AMP-activated protein kinase (AMPK). Whether metformin or the satiety factor leptin, which also stimulates AMPK in muscle, regulates this enzyme in pancreatic islets is unknown. We have recently shown that forced increases in AMPK activity inhibit insulin secretion from MIN6 cells (da Silva Xavier G, Leclerc I, Varadi A, Tsuboi T, Moule SK, and Rutter GA. Biochem J 371: 761–774, 2003). Here, we explore whether 1) glucose, metformin, or leptin regulates AMPK activity in isolated islets from rodent and human and 2) whether changes in AMPK activity modulate insulin secretion from human islets. Increases in glucose concentration from 0 to 3 and from 3 to 17 mM inhibited AMPK activity in primary islets from mouse, rat, and human, confirming previous findings in insulinoma cells. Incubation with metformin (0.2–1 mM) activated AMPK in both human islets and MIN6 β-cells in parallel with an inhibition of insulin secretion, whereas leptin (10–100 nM) was without effect in MIN6 cells. These studies demonstrate that AMPK activity is subject to regulation by both glucose and metformin in pancreatic islets and clonal β-cells. The inhibitory effects of metformin on insulin secretion may therefore need to be considered with respect to the use of this drug for the treatment of type 2 diabetes.

Imaging Glucose-Regulated Insulin Secretion and Gene Expression in Single Islet β-Cells: Control by AMP-Activated Protein Kinase

2004 ◽  
Vol 40 (3S) ◽  
pp. 179-190 ◽  
Author(s):  
Guy A. Rutter ◽  
Isabelle Leclerc ◽  
Takashi Tsuboi ◽  
Gabriela da Silva Xavier ◽  
Frédérique Diraison ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Β Cells ◽  
Amp Activated Protein Kinase

scholarly journals AMP-activated protein kinase agonist dose dependently improves function and reduces apoptosis in glucotoxic β-cells without changing triglyceride levels

2008 ◽  
Vol 41 (3) ◽  
pp. 187-194 ◽  
Author(s):  
Hanna K Nyblom ◽  
Ernest Sargsyan ◽  
Peter Bergsten
Keyword(s):  
Protein Kinase ◽  
Cell Function ◽  
Β Cells ◽  
Β Cell ◽  
Downstream Target ◽  
Homologous Protein ◽  
Prolonged Culture ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion ◽  
Amp Activated Protein Kinase

Prolonged hyperglycaemia leads to impaired glucose-stimulated insulin secretion (GSIS) and apoptosis in insulin-producing β-cells. The detrimental effects have been connected with glucose-induced lipid accumulation in the β-cell. AMP-activated protein kinase (AMPK) agonist, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), promotes utilization of nutrient stores for energy production. It was tested how impaired GSIS and elevated apoptosis observed in insulinoma (INS)-1E cells after prolonged culture at 27 mM glucose were affected by the inclusion of 0.3 or 1 mM AICAR during culture. Glucose-induced impairment of insulin release was reverted by the inclusion of 0.3 but not 1 mM AICAR, which did not affect insulin content. The glucose-induced rise in triglyceride (TG) content observed in the cells cultured at 27 mM glucose was not altered by the inclusion of either 0.3 or 1 mM AICAR. Inclusion of 1 but not 0.3 mM AICAR during culture induced phosphorylation of AMPK and its downstream target acyl-CoA carboxylase. Phosphorylation was paralleled by reduced number of apoptotic cells and lowered expression of pro-apoptotic C/EBP homologous protein (CHOP). In conclusion, AICAR dose dependently improves β-cell function and reduces apoptosis in β-cells exposed to prolonged hyperglycaemia without changing TG levels.

Palmitate activates AMP-activated protein kinase and regulates insulin secretion from β cells

2007 ◽  
Vol 352 (2) ◽  
pp. 463-468 ◽  
Author(s):  
Xiao Wang ◽  
Libin Zhou ◽  
Guo Li ◽  
Tianhong Luo ◽  
Yanyun Gu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Β Cells ◽  
Amp Activated Protein Kinase

The PP1-R6 protein phosphatase holoenzyme is involved in the glucose-induced dephosphorylation and inactivation of AMP-activated protein kinase, a key regulator of insulin secretion, in MIN6 β cells

2010 ◽  
Vol 24 (12) ◽  
pp. 5080-5091 ◽  
Author(s):  
Luisa Garcia-Haro ◽  
Maria Adelaida Garcia-Gimeno ◽  
Dietbert Neumann ◽  
Monique Beullens ◽  
Mathieu Bollen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Phosphatase ◽  
Β Cells ◽  
Amp Activated Protein Kinase ◽  
Kinase A
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