scholarly journals Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway

2007 ◽  
Vol 195 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Muhammed Yusuf Ali ◽  
Matthew Whiteman ◽  
Chian-Ming Low ◽  
Philip K Moore
Keyword(s):  
Insulin Secretion ◽  
Hydrogen Sulphide ◽  
Recent Observation ◽  
Diabetic Rats ◽  
Β Cells ◽  
Naturally Occurring ◽  
Streptozotocin Diabetic Rats ◽  
Channel Dependent ◽  
Dependent Pathway ◽  
Insight Into

Hydrogen sulphide (H2S), a naturally occurring gas exerts physiological effects by opening KATP channels. Anti-diabetic drugs (e.g. glibenclamide) block KATP channels and abrogate H2S-mediated physiological responses which suggest that H2S may also regulate insulin secretion by pancreatic β-cells. To investigate this hypothesis, insulin-secreting (HIT-T15) cells were exposed to NaHS (100 μM) and the KATP channel-driven pathway of insulin secretion was tracked with various fluorescent probes. The concentration of insulin released from HIT-T15 cells decreased significantly after NaHS exposure and this effect was reversed by the addition of glibenclamide (10 μM). Cell viability and intracellular ATP and glutathione (GSH) levels remained unchanged, suggesting that changes in insulin secretion were not ATP linked or redox dependent. Through fluorescence imaging studies, it was found that K+ efflux occurs in cells exposed to NaHS. The hyperpolarised cell membrane, a result of K+ leaving the cell, prevents the opening of voltage-gated Ca2+ channels. This subsequently prevents Ca2+ influx and the release of insulin from HIT-T15 cells. This data suggest that H2S reduces insulin secretion by a KATP channel-dependent pathway in HIT-T15 cells. This study reports the molecular mechanism by which H2S reduces insulin secretion and provides further insight into a recent observation of increased pancreatic H2S production in streptozotocin-diabetic rats.

Effect of benfluorex on insulin secretion and insulin action in streptozotocin-diabetic rats

1993 ◽  
Vol 9 (S1) ◽  
pp. 57S-63S ◽  
Author(s):  
Bernard Portha ◽  
Patricia Serradas ◽  
Danielle Bailbé ◽  
Olivier Blondel ◽  
Françoise Picarel
Keyword(s):  
Insulin Secretion ◽  
Insulin Action ◽  
Diabetic Rats ◽  
Streptozotocin Diabetic Rats

scholarly journals Metabolic cycling in control of glucose-stimulated insulin secretion

2008 ◽  
Vol 295 (6) ◽  
pp. E1287-E1297 ◽  
Author(s):  
Mette V. Jensen ◽  
Jamie W. Joseph ◽  
Sarah M. Ronnebaum ◽  
Shawn C. Burgess ◽  
A. Dean Sherry ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Β Cells ◽  
Pyruvate Metabolism ◽  
Coupling Factors ◽  
Stimulus Secretion Coupling ◽  
Channel Dependent ◽  
Glucose Stimulated Insulin Secretion ◽  
Dependent Mechanism

Glucose-stimulated insulin secretion (GSIS) is central to normal control of metabolic fuel homeostasis, and its impairment is a key element of β-cell failure in type 2 diabetes. Glucose exerts its effects on insulin secretion via its metabolism in β-cells to generate stimulus/secretion coupling factors, including a rise in the ATP/ADP ratio, which serves to suppress ATP-sensitive K+ (KATP) channels and activate voltage-gated Ca2+ channels, leading to stimulation of insulin granule exocytosis. Whereas this KATP channel-dependent mechanism of GSIS has been broadly accepted for more than 30 years, it has become increasingly apparent that it does not fully describe the effects of glucose on insulin secretion. More recent studies have demonstrated an important role for cyclic pathways of pyruvate metabolism in control of insulin secretion. Three cycles occur in islet β-cells: the pyruvate/malate, pyruvate/citrate, and pyruvate/isocitrate cycles. This review discusses recent work on the role of each of these pathways in control of insulin secretion and builds a case for the particular relevance of byproducts of the pyruvate/isocitrate cycle, NADPH and α-ketoglutarate, in control of GSIS.

scholarly journals Glucose triggers protein kinase A-dependent insulin secretion in mouse pancreatic islets through activation of the K+ATP channel-dependent pathway

2005 ◽  
Vol 152 (4) ◽  
pp. 671-677 ◽  
Author(s):  
Peter Thams ◽  
Mohammad R Anwar ◽  
Kirsten Capito
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Adenylyl Cyclase ◽  
Pancreatic Islets ◽  
Mouse Pancreatic Islets ◽  
Channel Dependent ◽  
Dependent Pathway ◽  
Cyclase Activator ◽  
Kinase A

Objective: To assess the significance of protein kinase A (PKA) in glucose triggering of ATP-sensitive K+ (K+ATP) channel-dependent insulin secretion and in glucose amplification of K+ATP channel-independent insulin secretion. Methods: Insulin release from cultured perifused mouse pancreatic islets was determined by radioimmunoassay. Results: In islets cultured at 5.5 mmol/l glucose, and then perifused in physiological Krebs–Ringer medium, the PKA inhibitors, H89 (10 μmol/l) and PKI 6–22 amide (30 μmol/l) did not inhibit glucose (16.7 mmol/l)-induced insulin secretion, but inhibited stimulation by the adenylyl cyclase activator, forskolin (10 μmol/l). In the presence of 60 mmol/l K+ and 250 μmol/l diazoxide, which stimulates maximum Ca2+ influx independently of K+ATP channels, H89 (10 μmol/l) inhibited Ca2+-evoked insulin secretion, but failed to prevent glucose amplification of K+ATP channel-independent insulin secretion. In the presence of 1 mmol/l ouabain and 250 μmol/l diazoxide, which cause modest Ca2+ influx, glucose amplification of K+ATP channel-independent insulin secretion was observed without concomitant Ca2+ stimulation of PKA activity. In islets cultured at 16.7 mmol/l glucose, glucose (16.7 mmol/l)-induced insulin secretion in physiological Krebs–Ringer medium was augmented and now inhibited by H89 (10 μmol/l), implicating that culture at 16.7 mmol/l glucose may increase Ca2+-sensitive adenylyl cyclase activity and hence PKA activity. In accordance, Ca2+-evoked insulin secretion at 60 mmol/l K+ and 250 μmol/l diazoxide was improved, whereas glucose amplification of K+ATP channel-independent insulin secretion was unaffected. Conclusions: Glucose may activate PKA through triggering of the K+ATP channel-dependent pathway. Glucose amplification of K+ATP channel-independent insulin secretion, on the other hand, occurs by PKA-independent mechanisms.

Naringin (4′,5,7-Trihydroxyflavanone 7-Rhamnoglucoside) Attenuates β-Cell Dysfunction in Diabetic Rats through Upregulation of PDX-1

2018 ◽  
Vol 206 (3) ◽  
pp. 133-143 ◽  
Author(s):  
Manickam Subramanian ◽  
Balaji Thotakura ◽  
Swathi Priyadarshini Chandra Sekaran ◽  
Ashok kumar Jyothi ◽  
Indumathi Sundaramurthi
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Insulin Secretion ◽  
Protein Expression ◽  
Serum Insulin ◽  
Diabetic Rats ◽  
Insulin Gene ◽  
Β Cells ◽  
Β Cell ◽  
Insulin Gene Expression

Background: Pancreatic duodenal homeobox-1 (PDX-1) is a key transcription factor which regulates Insulin gene expression and insulin secretion in adult β-cells and helps to maintain β-cells mass. Naringin, a flavanone, owing to its anti­oxidant property, is reported to have antidiabetic effects. Objectives: The present study tries to evaluate the role of naringin on the β-cell-specific transcription factor PDX-1 in diabetic rats. Methods: Diabetes was induced in male rats using streptozotocin and treated with naringin (100 mg/kg) orally for 4 and 8 weeks. Serum insulin level, Pdx-1 and Insulin gene expression, and PDX-1 protein expression were assessed in the rat pancreas. Histopathological and ultrastructural changes in the islet and β-cells were observed. Results: Naringin prevented leukocytic infiltration in the pancreas of diabetic rats and recouped the β-cells with adequate secretory granules. Naringin-treated diabetic rats showed significantly increased mRNA expression of Pdx-1 and Insulin genes, increased expression of transcription factor PDX-1, and higher serum insulin levels than the diabetic control animals. These changes were more pronounced in the 8-week naringin-treated diabetic animals. Conclusions: Naringin was found to be an effective antidiabetic agent which increased Insulin gene expression and insulin secretion by upregulating the PDX-1 gene and protein expression.

Sign in / Sign up

Export Citation Format

Share Document