Chromatographic resolution and kinetic characterization of glucokinase from islets of Langerhans.

Meglasson, M. D.; Burch, Pamela Trueheart; Berner, Donna K; Najafi, Habiba; Vogin, Alan P.; Matschinsky, Franz M.

doi:10.1073/pnas.80.1.85

Cited by 80 publications

(41 citation statements)

References 29 publications

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“…The glucose Km of islet glucokinase in all the animals ranged from 8 to 19 mM (Table IV). The V. of glucokinase in control animals ranged from 103 to 142 mmol/kg dry tissue per h, which is equivalent to 5.15 to 7.10 mol/kg DNA per h using a factor of 20 ng DNA/ tig dry islet tissue (27). These values are similar to previous results obtained with a fluorometric method in rat islet isolated by a collagenase procedure ( 13,28).…”

Section: Resultssupporting

confidence: 81%

In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents.

Liang¹,

Bonner-Weir²,

Wu³

et al. 1994

J. Clin. Invest.

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The present study evaluated the involvement of glucose transport and phosphorylation in glucose-stimulated insulin release from pancreatic islets. Using quantitative histochemical techniques, we investigated basal islet glucose content, islet glucose uptake in situ during acute extreme experimental hyperglycemia, and islet glucokinase activity in several animal models of diabetes and obesity. The basal islet glucose content in anaesthetized diabetic or obese rodents was either the same or higher than that in their relevant controls. The rate of glucose uptake of islet tissue in these animals after an i.v. glucose injection was different. The db+/db+ mouse and the obese Zucker rat exhibited significantly reduced islet glucose uptake rates. RIP-cHras transgenic mice, BHE/cdb rats and partially pancreatectomized rats showed normal islet glucose uptake rates. The activity of islet glucokinase was increased to a different degree related to the blood glucose level. All five animal models of diabetes or obesity exhibited either a delay or a reduction of insulin release in response to supra maximal glucose stimulation. Our results indicate that the impairment of glucose-induced insulin release in diabetes is not consistently associated with a reduction of islet glucose uptake nor a change of glucokinase activity. (J. Clin. Invest. 1994. 93:2473-2481.) Key words: diabetic animal -glucokinase * GLUT2 * insulin releasepancreatic islet Introduction Under physiological conditions, pancreatic (3 cells sense the change ofblood glucose level and adjust insulin output accordingly. The mechanism ofglucose sensing by (3 cells is, however, still unclear. There are two candidates for glucose sensors in pancreatic islets: the glucose transporter (GLUT2)' and gluco-

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Section: Resultssupporting

confidence: 81%

In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents.

Liang¹,

Bonner-Weir²,

Wu³

et al. 1994

J. Clin. Invest.

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“…The ability to prepare islet B cell subpopulations which differ in metabolic responsiveness to glucose, makes it feasible to compare glucose responsive and unresponsive subpopulations for the expression and activities ofpotential key regulators such as the liver-type glucose transporter ( 17), glucokinase ( 18,19), or other glucose-induced signals (20,21 (22,23). We have, so far, not detected any inhibition in the rate of proinsulin conversion in the high responsive cells, so that their higher content in pale granules may be related to the higher state ofbiosynthetic activity in these cells.…”

Section: Discussionmentioning

confidence: 99%

Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity.

Kiekens¹,

Veld²,

Mahler³

et al. 1992

J. Clin. Invest.

155

154

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In vitro incubated rat islet B cells differ in their individual rates of protein synthesis. The number of cells in biosynthetic activity increases with the glucose concentration. Flow cytometric monitoring of the cellular redox states indicated that islet B cells differ in their individual metabolic responsiveness to glucose. A shift from basal to increased NAD(P)H fluorescence occurred for 18% of the cells at 1 mM glucose, for 43% at 5 mM, and for 70% at 20 mM. The functional significance of this metabolic heterogeneity was assessed by comparing protein synthesis in metabolically responsive and unresponsive subpopulations, shortly after their separation by autofluorescenceactivated cell sorting. The glucose-sensitive subpopulation exhibited four-to fivefold higher rates of insulin synthesis during 60-min incubations at 2.5-10 mM glucose. Its higher biosynthetic activity was mainly caused by recruitment of cells into active synthesis and, to a lesser extent, by higher biosynthetic activity per recruited cell. Cells from the glucose-sensitive subpopulation were larger, and presented a threefold higher density of a pale secretory vesicle subtype, which is thought to contain unprocessed proinsulin. It is concluded that intercellular differences in metabolic responsiveness result in functional heterogeneity of the pancreatic B cell population. (J. Clin. Invest. 1992. 89:117-125.)

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“…The findings were 1) D-mannoheptulose inhibits insulin release induced by glucose and mannose but not that induced by tolbutamide [8,10] 2) D-mannoheptulose inhibits rat or rabbit liver GK (Ki i mmol/1) and HKs [6,11] and glucose uptake by rat liver [11] 3) phloridzin, D-galactose and 3-0-methyl-D-glucose (inhibitors of glucose-transport) do not inhibit glucose-induced insulin release [7,8] whereas Dglucosamine which inhibits GK (Ki 0.5 mmol/1) [6] is inhibitory [8]. In 1968 Matschinsky and Ellerman [12] confirmed this conclusion by direct analysis of islet glucose, and the presence of HKs in islet extracts with low and high Km for glucose was shown by them and by Ashcrofl and Randle [12][13][14][15]. The definitive evidence for the presence of GK protein in pancreatic islets was obtained by immuno-blotting and by the detection of mRNA (Iynedjian and co-workers [16,17]); by immunocytochemical localisation to islet beta cells [18]; and by isolation and sequence analysis of full length cDNA by Magnuson, Permutt and colleagues [18][19][20] (this latter method has revealed structural differences between liver and islet GKs which are discussed later).…”

Section: Discovery Of Pancreatic Islet Glucokinasementioning

confidence: 99%

Glucokinase and candidate genes for Type 2 (non-insulin-dependent) diabetes mellitus

Randle

1993

Diabetologia

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Chromatographic resolution and kinetic characterization of glucokinase from islets of Langerhans.

Cited by 80 publications

References 29 publications

In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents.

In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents.

Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity.

Glucokinase and candidate genes for Type 2 (non-insulin-dependent) diabetes mellitus

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