Pancreatic beta cell CASK gene knockout aggravates beta cell aging and abnormal glucose metabolism in old mice

beta-Cell function and glucose metabolism were studied in eight insulin-dependent diabetic recipients of combined segmental pancreas and kidney transplant with peripheral insulin delivery (Px), in eight nondiabetic kidney-transplant individuals (Kx), and in eight normal subjects (Ns) after three consecutive mixed meals. All subjects had normal fasting plasma glucose, but increased basal levels of C-peptide were demonstrated in the transplant groups (P < 0.05 relative to Ns). Postprandial hyperglycemia was increased 14% in Kx and 32% in Px (P < 0.05), whereas compared with Ns postprandial C-peptide levels were increased three- and twofold, respectively, in Kx and Px (P < 0.05). Compared with Ns basal insulin secretion rate (combined model) was increased 2-fold in Kx and 1.4-fold in Px (P < 0.05). Maximal insulin secretion rate was reduced 25% in Px compared with Kx (P < 0.05) but not different from that of Ns (P NS). Also, maximal insulin secretion rate occurred later in Px than in controls (Tmax: Px 50 min, Kx 30 min, and Ns 32 min; P < 0.05). The total integrated insulin secretion was increased 1.4-fold in Px compared with Ns (P < 0.05) but decreased 1.4-fold compared with Kx (P < 0.05). Fasting and postprandial proinsulin-to-C-peptide molar ratios were inappropriately increased in Px compared with Kx and Ns. Basal hepatic glucose production was increased 43% in Px and 33% in Kx compared with Ns (P < 0.05). Postprandial total systemic glucose appearance was similar in all three groups, whereas peripheral glucose disposal was 15% reduced in Px (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Pancreatic beta cell line MIN6 exhibits characteristics of glucose metabolism and glucose-stimulated insulin secretion similar to those of normal islets

Diabetologia ◽

10.1007/bf00401058 ◽

1993 ◽

Vol 36 (11) ◽

pp. 1139-1145 ◽

Cited By ~ 268

Author(s):

H. Ishihara ◽

T. Asano ◽

K. Tsukuda ◽

H. Katagiri ◽

K. Inukai ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Metabolism ◽

Beta Cell ◽

Cell Line ◽

Pancreatic Beta Cell ◽

Beta Cell Line ◽

Glucose Stimulated Insulin Secretion

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Glucose metabolism and insulin release in mouse beta HC9 cells, as model for wild-type pancreatic beta-cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.5.e846 ◽

1996 ◽

Vol 270 (5) ◽

pp. E846-E857 ◽

Cited By ~ 14

Author(s):

Y. Liang ◽

G. Bai ◽

N. Doliba ◽

C. Buettger ◽

L. Wang ◽

...

Keyword(s):

Glucose Metabolism ◽

Beta Cell ◽

Cell Line ◽

Insulin Release ◽

Cell Lines ◽

Pancreatic Beta Cells ◽

Pancreatic Beta Cell ◽

Glucose Sensing ◽

Cell Functions ◽

Glucose Phosphorylation

Glucose metabolism and its relationship with glucose-induced insulin release were studied in beta HC9 and beta TC3 cells to identify and characterize key factors controlling the intermediary metabolism of glucose and glucose-induced insulin release. The beta HC9 cell line, derived from pancreatic islets with beta-cell hyperplasia, is characterized by a normal concentration-dependency curve for glucose-stimulated insulin release, whereas the beta TC3 cell line, derived from pancreatic beta-cell tumors, shows a marked leftward shift of this curve. Maximum velocity and the Michaelis-Menten constant of glucose uptake in beta HC9 and beta TC3 cells were similar, even though GLUT-2 expression in these two cell lines differed. In both cell lines, the kinetic characteristics of glucose usage, glucose oxidation, and glucose-induced oxygen consumption were similar to those of glucose phosphorylation, indicating that the kinetics of glucose metabolism from the glucose phosphorylation step in the cytosol to the mitochondrial process of oxidative phosphorylation are determined by the glucose-phosphorylating enzyme, that is, by glucokinase in beta HC9 cells and by hexokinase in beta TC3 cells. Thus beta HC9 cells provide an opportunity for the quantitative analysis of glucose metabolism, the associated generation of coupling factors, and other essential beta-cell functions involved in glucose sensing and insulin secretion.

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Pancreatic Beta Cell Glucose Metabolism and Glibenclamide-lnduced Insulin Release

Hormone and Metabolic Research ◽

10.1055/s-0028-1093779 ◽

1975 ◽

Vol 7 (01) ◽

pp. 10-15 ◽

Cited By ~ 1

Author(s):

J. Basabe ◽

Josefina Farina ◽

R. Chieri

Keyword(s):

Glucose Metabolism ◽

Beta Cell ◽

Insulin Release ◽

Pancreatic Beta Cell ◽

Cell Glucose

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ATP-sensitive K+ channel-independent glucose action in rat pancreatic beta-cell

AJP Cell Physiology ◽

10.1152/ajpcell.1994.266.3.c622 ◽

1994 ◽

Vol 266 (3) ◽

pp. C622-C627 ◽

Cited By ~ 55

Author(s):

T. Aizawa ◽

Y. Sato ◽

F. Ishihara ◽

N. Taguchi ◽

M. Komatsu ◽

...

Keyword(s):

Glucose Metabolism ◽

Beta Cell ◽

Phospholipase C ◽

Insulin Release ◽

Islet Cells ◽

Pancreatic Beta Cell ◽

Cytosolic Calcium ◽

Sweet Taste ◽

K Channel ◽

Glucose Molecule

The nature of ATP-sensitive K+ (K+ATP) channel-independent, insulinotropic action of glucose was investigated using non-glucose-primed pancreatic islets. When the beta-cell was depolarized with K+, glucose dose dependently stimulated insulin release despite inhibition of the K+ATP channel closure by diazoxide. K+ depolarization could be replaced with BAY K 8644, a calcium channel agonist. Prior fasting of rats and lowering ambient temperature greatly suppressed glucose oxidation and utilization by the islet cells and abolished insulin release in response to high glucose alone. However, under these conditions, the K+ATP channel-independent, glucose-induced insulin release was clearly demonstrable. p-Nitrophenyl-alpha-D-glucopyranoside (sweet taste inhibitor) but not its beta-isomer, neomycin (phospholipase C inhibitor) and staurosporine (C kinase blocker) inhibited the K+ATP channel-independent, insulinotropic action of glucose. For the K+ATP channel-independent glucose-induced insulin release 1) elevation of cytosolic calcium is required, 2) minute glucose metabolism is enough, if glucose metabolism is necessary, and 3) direct recognition of glucose molecule, phospholipase C, and protein kinase C appear to be involved.

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13C NMR analysis reveals a link between L-glutamine metabolism, D-glucose metabolism and ?-glutamyl cycle activity in a clonal pancreatic beta-cell line

Diabetologia ◽

10.1007/s00125-003-1184-7 ◽

2003 ◽

Vol 46 (11) ◽

pp. 1512-1521 ◽

Cited By ~ 47

Author(s):

L. Brennan ◽

M. Corless ◽

C. Hewage ◽

J. P. G. Malthouse ◽

N. H. McClenaghan ◽

...

Keyword(s):

Glucose Metabolism ◽

Beta Cell ◽

Cell Line ◽

13C Nmr ◽

Pancreatic Beta Cell ◽

Glutamine Metabolism ◽

Nmr Analysis ◽

13C Nmr Analysis ◽

Beta Cell Line

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Pancreatic beta-cell specific deletion of ABCA1 and ABCG1 perturbs glucose metabolism and increases adiposity in mice due to suboptimal plasma insulin levels

Atherosclerosis ◽

10.1016/j.atherosclerosis.2015.04.028 ◽

2015 ◽

Vol 241 (1) ◽

pp. e3

Author(s):

B.J. Cochran ◽

L. Hou ◽

A.P. Chirackal Manavalan ◽

A. Sultana ◽

B.M. Moore ◽

...

Keyword(s):

Glucose Metabolism ◽

Beta Cell ◽

Plasma Insulin ◽

Pancreatic Beta Cell ◽

Insulin Levels ◽

Plasma Insulin Levels ◽

Specific Deletion

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Mathematical model of beta-cell glucose metabolism and insulin release. I. Glucokinase as glucosensor hypothesis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.4.e775 ◽

1995 ◽

Vol 268 (4) ◽

pp. E775-E788 ◽

Cited By ~ 4

Author(s):

I. R. Sweet ◽

F. M. Matschinsky

Keyword(s):

Mathematical Model ◽

Glucose Metabolism ◽

Beta Cell ◽

Simulation Analysis ◽

Pancreatic Beta Cell ◽

Experimental Tests ◽

Glucose Sensing ◽

Potential Control ◽

Cell Glucose ◽

Tests Of Hypotheses

To quantitatively test the theory that glucokinase controls the rate of glucose metabolism and therefore the rate of insulin secretion, a minimal mathematical model of glycolysis in the pancreatic beta-cell was developed. The model represents our current hypothesis of how the normal beta-cell transduces the glucose signal. In this report, the model was used to address questions regarding the control strength of transport, hexokinase, glucose-6-phosphatase, and phosphofructokinase in the metabolism of glucose. The hypothesis that fructose 6-phosphate and a protein regulator modulate glucokinase activity was evaluated by simulation analysis, as was the possibility that glucose-6-phosphatase, working in concert with phosphofructokinase, can modulate the glucose-sensing system. It was found that, in the absence of glucose-6-phosphatase, transport, hexokinase, and phosphofructokinase do not greatly influence the rate of glucose metabolism unless their activities are dramatically altered from the measured values. Glucose metabolism was profoundly affected by the activity of glucokinase. However, in the presence of glucose-6-phosphatase, the ratio of glucose-6-phosphatase to phosphofructokinase activities was a very important parameter, and this potential control mechanism deserves more attention. The results further support the notion that glucokinase is indeed the glucosensor of the beta-cell and that modeling the system in toto provides quantitative evaluation needed to interpret the experimental tests of hypotheses.

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