Hexamminecobalt(III) Chloride Inhibits Glucose-induced Insulin Secretion at the Exocytotic Process

Tsubamoto, Yoshiharu; Eto, Kazuhiro; Noda, Mitsuhiko; Daniel, Samira; Suga, Sechiko; Yamashita, Satoshi; Kasai, Hideaki; Wakui, Makoto; Sharp, Geoffrey W. G.; Kimura, Satoshi; Kadowaki, Takashi

doi:10.1074/jbc.m005816200

Cited by 8 publications

(6 citation statements)

References 50 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, the ready releasable pool has been quantitated by immunologic detection of the docking complex and shown to be responsible for KCl-induced insulin release as well as the first phase of GSIS [132]. Inhibition of GSIS by hexamminecobalt (III) chloride, which was found to act by stabilizing the docking complex, is consistent with this conclusion [133].…”

Section: Calcium Influx and Stimulation Of Exocytosissupporting

confidence: 71%

Fatty acid metabolism and insulin secretion in pancreatic beta cells

2003

View full text Add to dashboard Cite

Increases in glucose or fatty acids affect metabolism via changes in long-chain acyl-CoA formation and chronically elevated fatty acids increase total cellular CoA. Understanding the response of pancreatic beta cells to increased amounts of fuel and the role that altered insulin secretion plays in the development and maintenance of obesity and Type 2 diabetes is important. Data indicate that the activated form of fatty acids acts as an effector molecule in stimulus-secretion coupling. Glucose increases cytosolic long-chain acylCoA because it increases the "switch" compound malonyl-CoA that blocks mitochondrial β-oxidation, thus implementing a shift from fatty acid to glucose oxidation. We present arguments in support of the following: (i) A source of fatty acid either exogenous or endogenous (derived by lipolysis of triglyceride) is necessary to support normal insulin secretion; (ii) a rapid increase of fatty acids potentiates glucose-stimulated secretion by increasing fatty acyl-CoA or complex lipid concentrations that act distally by modulating key enzymes such as protein kinase C or the exocytotic machinery; (iii) a chronic increase of fatty acids enhances basal secretion by the same mechanism, but promotes obesity and a diminished response to stimulatory glucose; (iv) agents which raise cAMP act as incretins, at least in part, by stimulating lipolysis via beta-cell hormone-sensitive lipase activation. Furthermore, increased triglyceride stores can give higher rates of lipolysis and thus influence both basal and stimulated insulin secretion. These points highlight the important roles of NEFA, LC-CoA, and their esterified derivatives in affecting insulin secretion in both normal and pathological states. [Diabetologia (2003[Diabetologia ( ) 46:1297[Diabetologia ( -1312

show abstract

Section: Calcium Influx and Stimulation Of Exocytosissupporting

confidence: 71%

Fatty acid metabolism and insulin secretion in pancreatic beta cells

2003

View full text Add to dashboard Cite

show abstract

“…The contents of ATP and cAMP in the red gastrocnemius were determined as described previously . ATP and cAMP contents in the supernatant were measured using a bioluminescent assay kit and an enzyme‐linked immunoassay kit (Cat# A095‐1 and Cat# H164; Nanjing Jiancheng Bioengineering institute, Nanjing, China), respectively.…”

Section: Methodsmentioning

confidence: 99%

6‐Gingerol Improves Ectopic Lipid Accumulation, Mitochondrial Dysfunction, and Insulin Resistance in Skeletal Muscle of Ageing Rats: Dual Stimulation of the AMPK/PGC‐1α Signaling Pathway via Plasma Adiponectin and Muscular AdipoR1

Liu

Yao

Wang

et al. 2019

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope This study investigates the dual actions of 6‐gingerol in stimulating both plasma adiponectin and muscular adiponectin receptor signaling in naturally ageing rats. Methods and results Twenty‐two‐month‐old male SD rats were treated with 6‐gingerol (0.2 mg kg–1, once daily) for 7 weeks. 6‐Gingerol can attenuate age‐associated high plasma triglyceride, glucose, and insulin concentrations under fasting conditions as well as suppress the increase in the HOMA‐IR index and inhibit the decrease of muscular p‐Akt/Akt protein in ageing rats, which indicates an improvement of systemic and muscular insulin sensitivity. Accompanying these changes, treatment with 6‐gingerol attenuates excessive triglyceride accumulation, enhances mitochondrial function, and promotes a transition from a fast‐ to slow‐fiber type and muscle oxidative metabolism in the red gastrocnemius of ageing rats. More importantly, 6‐gingerol not only increases the plasma and adipose tissue adiponectin concentrations, but also elevates muscular AdipoR1 expression and activates downstream AMPK phosphorylation as well as upregulates PGC‐1α in vivo and in vitro. Conclusion 6‐Gingerol may improve ectopic lipid accumulation, mitochondrial dysfunction, and insulin resistance in skeletal muscle of ageing rats. These effects rely, at least in part, on the elevated plasma adiponectin concentration and muscle AdipoR1 level to dually activate the AMPK/PGC‐1α signaling pathway.

show abstract

“…Thus we next measured ATP content of islets (Fig. 4B) (54). Stimulation of islets with 22.2 mM glucose significantly increased ATP content from 10.2 Ϯ 0.4 to 13.9 Ϯ 1.2 pmol/islet.…”

Section: Glucose Acutely Alkalinizes Secretory Vesicle Phmentioning

confidence: 99%

“…Islets were isolated by collagenase digestion and manual picking from the pancreata of C57BL6J mice at 3-4 mo old (54). These islets were used for experiments immediately after isolation.…”

Section: Materials Insulin Radioimmunoassay Kit and [U-mentioning

confidence: 99%

See 1 more Smart Citation

Glucose metabolism and glutamate analog acutely alkalinize pH of insulin secretory vesicles of pancreatic β-cells

Eto¹,

Yamashita

Hirose³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

. Glucose metabolism and glutamate analog acutely alkalinize pH of insulin secretory vesicles of pancreatic ␤-cells. Am J Physiol Endocrinol Metab 285: E262-E271, 2003. First published March 18, 2003 10.1152/ajpendo.00542.2002We studied acute changes of secretory vesicle pH in pancreatic ␤-cells with a fluorescent pH indicator, lysosensor green DND-189. Fluorescence was decreased by 0.66 Ϯ 0.10% at 149 Ϯ 16 s with 22.2 mM glucose stimulation, indicating that vesicular pH was alkalinized by ϳ0.016 unit. Glucose-responsive pH increase was observed when cytosolic Ca 2ϩ influx was blocked but disappeared when an inhibitor of glycolysis or mitochondrial ATP synthase was present. Glutamate dimethyl ester (GME), a plasma membrane-permeable analog of glutamate, potentiated glucose-stimulated insulin secretion at 5 mM without changing cellular ATP content or cytosolic Ca 2ϩ concentration ([Ca 2ϩ ]). Application of GME at basal glucose concentration decreased DND-189 fluorescence by 0.83 Ϯ 0.19% at 38 Ϯ 2 s. These results indicated that the acutely alkalinizing effect of glucose on ␤-cell secretory vesicle pH was dependent on glucose metabolism but independent of modulations of cytosolic [Ca 2ϩ ]. Moreover, glutamate derived from glucose may be one of the mediators of this alkalinizing effect of glucose, which may have potential relevance to the alteration of secretory function by glutamate. glutamate metabolism; alkalinization of vesicular pH; regulation of insulin secretion INSULIN SECRETION from pancreatic ␤-cells in response to extracellular glucose is essential for maintenance of systemic glucose homeostasis. Although a pathway to trigger Ca 2ϩ influx into the cytosol via glucose metabolism, ATP generation, and a closure of the ATP-sensitive potassium (K ATP ) channels is of prime importance for glucose-stimulated insulin secretion (5,16, 31,56), this central paradigm cannot explain some aspects of the secretory pathway. Thus it is known that an increase in glucose concentrations further enhances insulin secretion when cytosolic Ca 2ϩ concentration ([Ca 2ϩ ]) is fixed at higher levels in the presence of depolarizing concentration of KCl and the K ATP channel opener diazoxide (19,45). Moreover, in ␤-cells that were permeabilized with ␣-toxin and exposed to relatively high cytosolic [Ca 2ϩ ] and ATP concentration ([ATP]), substrates for the mitochondrial tricarboxylic acid (TCA) cycle induced a substantial increase in insulin secretion (28). These results indicate that metabolic derivatives from the TCA cycle might positively modulate glucosestimulated insulin secretion. Lipid metabolites synthesized from glucose-derived citrate through acetyl-CoA and malonyl-CoA are among the intriguing molecular candidates for this potentiation mechanism (12,40,41).Recently, two important findings were reported regarding a relationship between glutamate metabolism and insulin secretion. A new form of persistent hyperinsulinemia with hypoglycemia of the infant (PHHI) was demonstrated to be caused by an excessive activity ...

show abstract

Hexamminecobalt(III) Chloride Inhibits Glucose-induced Insulin Secretion at the Exocytotic Process

Cited by 8 publications

References 50 publications

Fatty acid metabolism and insulin secretion in pancreatic beta cells

Fatty acid metabolism and insulin secretion in pancreatic beta cells

6‐Gingerol Improves Ectopic Lipid Accumulation, Mitochondrial Dysfunction, and Insulin Resistance in Skeletal Muscle of Ageing Rats: Dual Stimulation of the AMPK/PGC‐1α Signaling Pathway via Plasma Adiponectin and Muscular AdipoR1

Glucose metabolism and glutamate analog acutely alkalinize pH of insulin secretory vesicles of pancreatic β-cells

Contact Info

Product

Resources

About