scholarly journals 13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS)

2002 ◽  
Vol 99 (5) ◽  
pp. 2708-2713 ◽  
Author(s):  
D. Lu ◽  
H. Mulder ◽  
P. Zhao ◽  
S. C. Burgess ◽  
M. V. Jensen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
13C Nmr ◽  
Pyruvate Cycling ◽  
Isotopomer Analysis ◽  
Glucose Stimulated Insulin Secretion

scholarly journals β-Cell-specific pyruvate dehydrogenase deficiency impairs glucose-stimulated insulin secretion

2010 ◽  
Vol 299 (6) ◽  
pp. E910-E917 ◽  
Author(s):  
Malathi Srinivasan ◽  
Cheol S. Choi ◽  
Pushpankur Ghoshal ◽  
Lioudmila Pliss ◽  
Jignesh D. Pandya ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Mouse Model ◽  
Pyruvate Dehydrogenase ◽  
Isolated Islets ◽  
Male Mice ◽  
Β Cells ◽  
Β Cell ◽  
Pyruvate Cycling ◽  
Glucose Stimulated Insulin Secretion

Glucose-stimulated insulin secretion (GSIS) by β-cells requires the generation of ATP from oxidation of pyruvate as well as generation of coupling factors involving three different pyruvate cycling shuttles. The roles of several key enzymes involved in pyruvate cycling in β-cells have been documented using isolated islets and β-cell clonal lines. To investigate the role of the pyruvate dehydrogenase (PDH) complex (PDC) in GSIS, a murine model of β-cell-specific PDH deficiency (β-PDHKO) was created. Pancreatic insulin content was decreased in 1-day-old β-PDHKO male pups and adult male mice. The plasma insulin levels were decreased and blood glucose levels increased in β-PDHKO male mice from neonatal life onward. GSIS was reduced in isolated islets from β-PDHKO male mice with about 50% reduction in PDC activity. Impairment in a glucose tolerance test and in vivo insulin secretion during hyperglycemic clamp was evident in β-PDHKO adults. No change in the number or size of islets was found in pancreata from 4-wk-old β-PDHKO male mice. However, an increase in the mean size of individual β-cells in islets of these mice was observed. These findings show a key role of PDC in GSIS by pyruvate oxidation. This β-PDHKO mouse model represents the first mouse model in which a mitochondrial oxidative enzyme deletion by gene knockout has been employed to demonstrate an altered GSIS by β-cells.

scholarly journals Role for malic enzyme, pyruvate carboxylation, and mitochondrial malate import in glucose-stimulated insulin secretion

2009 ◽  
Vol 296 (6) ◽  
pp. E1354-E1362 ◽  
Author(s):  
Emma Heart ◽  
Gary W. Cline ◽  
Leon P. Collis ◽  
Rebecca L. Pongratz ◽  
Joshua P. Gray ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Malic Enzyme ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Pyruvate Cycling ◽  
Mouse Islets ◽  
Glucose Stimulated Insulin Secretion ◽  
Interfering Rna ◽  
Rat Insulinoma

Pyruvate cycling has been implicated in glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. The operation of some pyruvate cycling pathways is proposed to necessitate malate export from the mitochondria and NADP+-dependent decarboxylation of malate to pyruvate by cytosolic malic enzyme (ME1). Evidence in favor of and against a role of ME1 in GSIS has been presented by others using small interfering RNA-mediated suppression of ME1. ME1 was also proposed to account for methyl succinate-stimulated insulin secretion (MSSIS), which has been hypothesized to occur via succinate entry into the mitochondria in exchange for malate and subsequent malate conversion to pyruvate. In contrast to rat, mouse β-cells lack ME1 activity, which was suggested to explain their lack of MSSIS. However, this hypothesis was not tested. In this report, we demonstrate that although adenoviral-mediated overexpression of ME1 greatly augments GSIS in rat insulinoma INS-1 832/13 cells, it does not restore MSSIS, nor does it significantly affect GSIS in mouse islets. The increase in GSIS following ME1 overexpression in INS-1 832/13 cells did not alter the ATP-to-ADP ratio but was accompanied by increases in malate and citrate levels. Increased malate and citrate levels were also observed after INS-1 832/13 cells were treated with the malate-permeable analog dimethyl malate. These data suggest that although ME1 overexpression augments anaplerosis and GSIS in INS-1 832/13 cells, it is not likely involved in MSSIS and GSIS in pancreatic islets.

scholarly journals A Pyruvate Cycling Pathway Involving Cytosolic NADP-dependent Isocitrate Dehydrogenase Regulates Glucose-stimulated Insulin Secretion

2006 ◽  
Vol 281 (41) ◽  
pp. 30593-30602 ◽  
Author(s):  
Sarah M. Ronnebaum ◽  
Olga Ilkayeva ◽  
Shawn C. Burgess ◽  
Jamie W. Joseph ◽  
Danhong Lu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Isocitrate Dehydrogenase ◽  
Pyruvate Cycling ◽  
Glucose Stimulated Insulin Secretion

Synchronized Microfluidic System to Dynamically Assess Pancreatic Islet Function beyond Glucose-Stimulated Insulin Secretion

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2162-P
Author(s):  
STEPHAN NIEUWOUDT ◽  
RUTH MCDOWELL ◽  
HUI ZHANG ◽  
JOHN P. KIRWAN
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Microfluidic System ◽  
Islet Function ◽  
Glucose Stimulated Insulin Secretion

scholarly journals In Vitro Studies to Assess the α-Glucosidase Inhibitory Activity and Insulin Secretion Effect of Isorhamnetin 3-O-Glucoside and Quercetin 3-O-Glucoside Isolated from Salicornia herbacea

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 483
Author(s):  
Dahae Lee ◽  
Jun Yeon Park ◽  
Sanghyun Lee ◽  
Ki Sung Kang
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Ethanolic Extract ◽  
Ethyl Acetate Fraction ◽  
Gradient Elution ◽  
Glucosidase Activity ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion ◽  
Salicornia Herbacea

In this study, we examined the effect of ethanolic extract of Salicornia herbacea (ESH), isorhamnetin 3-O-glucoside (I3G), quercetin 3-O-glucoside (Q3G), quercetin, and isorhamnetin on α-glucosidase activity and glucose-stimulated insulin secretion (GSIS) in insulin-secreting rat insulinoma (INS-1) cells. A portion of the ethyl acetate fraction of ESH was chromatographed on a silica gel by a gradient elution with chloroform and methanol to provide Q3G and I3G. ESH, Q3G, and quercetin inhibited α-glucosidase activity, and quercetin (IC50 value was 29.47 ± 3.36 μM) inhibited the activity more effectively than Q3G. We further demonstrated that ESH, Q3G, quercetin, I3G, and isorhamnetin promote GSIS in INS-1 pancreatic β-cells without inducing cytotoxicity. Among them, I3G was the most effective in enhancing GSIS. I3G enhanced the phosphorylation of total extracellular signal-regulated kinase (ERK), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and activated pancreatic and duodenal homeobox-1 (PDX-1), which are associated with insulin secretion and β-cell function. As components of ESH, Q3G has the potential to regulate blood glucose by inhibiting α-glucosidase activity, and I3G enhances the insulin secretion, but its bioavailability should be considered in determining biological importance.

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