Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression.

Vos, Anick De; Heimberg, Henry; Quartier, Erik; Huypens, Peter; Bouwens, Luc; Pipeleers, Daniël; Schuit, Franciscus

doi:10.1172/jci118308

Cited by 359 publications

(214 citation statements)

References 42 publications

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“…Such glucose dependence is consistent with the fact that high K m GLUT2 is the dominating glucose transporter in rodent β-cells Johnson et al, 1990). It was therefore unexpected that human β-cells preferentially express low K m GLUT1 (De Vos et al, 1995), whose capacity is close to saturation already at threshold concentrations of glucose. However, consistent with the latter observation, transgenic re-expression of GLUT1 or GLUT2 into β-cells of GLUT2-null mice were equally efficient in restoring normal glucose sensing (Thorens et al, 2000).…”

Section: Role Of Metabolism For Glucose-induced Insulin Secretionsupporting

confidence: 74%

Oscillatory control of insulin secretion

Tengholm

Gylfe

2009

Molecular and Cellular Endocrinology

162

169

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Pulsatile insulin secretionSince insulin is the only blood glucose-lowering hormone, its secretion is essential for glucose homeostasis, and disturbances are associated with glucose intolerance and diabetes.Glucose is the major stimulus for insulin release but secretion is enhanced also by other nutrients and is under stimulatory and inhibitory control by hormones and neurotransmitters.Although the external factors are essential determinants of insulin secretion, there are also input-independent variations in hormone release. Regular oscillations of the circulating insulin concentrations in normal subjects consequently occur without accompanying changes

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Section: Role Of Metabolism For Glucose-induced Insulin Secretionsupporting

confidence: 74%

Oscillatory control of insulin secretion

Tengholm

Gylfe

2009

Molecular and Cellular Endocrinology

162

169

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“…In this context it is notable that some genes share high expression in beta cells and the liver and are involved in metabolic regulation such as GLUT1/2 and glucokinase [48]. The high abundance of CaM kinase IIb and d mRNA could lead to the conclusion that these isoforms are important molecules in beta-cell physiology, compared with CaM kinase IIg, but this has to be proven.…”

Section: Discussionmentioning

confidence: 99%

Cloning and quantitative determination of the human Ca 2+ /calmodulin-dependent protein kinase II (CaMK II) isoforms in human beta cells

et al. 2000

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The Ca 2+ /calmodulin-dependent protein kinase II (CaMK II) is a multifunctional enzyme which is widely expressed from yeast to mammals and occurs in four different isoforms termed a, b, g and d which are derived from different genes [1,2]. The highest concentrations are in the CNS where the aisoform and b-isoform are involved in neurotransmitter release [1,2] whereas the g-isoform and disoform occur in most peripheral cells [3,4] and participate in control of cell cycle, metabolism, gene expression and membrane excitability. Insulin secretion in response to glucose and other nutrient stimuli is dependent on Ca 2+ and CaMK II seems to play an important part in this process [5±7]. Impairment of insulin secretion in response to glucose is an early event in the development of adult Type II (non-insulin-dependent) diabetes mellitus making it Diabetologia (2000) Abstract Aims/hypothesis. The Ca 2+ /calmodulin-dependent protein kinase II (CaMK II) is highly expressed in pancreatic islets and associated with insulin secretion vesicles. The suppression of CaMK II disturbs insulin secretion and insulin gene expression. There are four isoforms of CaMK II, a to d, that are expressed from different genes in mammals. Our aim was to identify the isoforms of CaMK II expressed in human beta cells by molecular cloning from a human insulinoma cDNA library and to assess its distribution in humans. Methods. The previously unknown complete coding sequences of human CaMK IIb and the kinase domain of CaMK IId were cloned from a human insulinoma cDNA library. Quantitative determination of CaMK II isoform mRNA was carried out in several tissues and beta cells purified by fluorescence activated cell sorting and compared to the housekeeping enzyme pyruvate dehydrogenase. Results. We found CaMK IIb occurred in three splice variants and was highly expressed in endocrine tissues such as adrenals, pituitary and beta cells. Liver showed moderate expression but adipose tissue or lymphocytes had very low levels of CaMK IIbmRNA. In human beta cells CaMK IIb and d were expressed equally with pyruvate dehydrogenase whereas tenfold lower expression of CaMK IIg and no expression of CaMK IIa were found. Conclusion/interpretation. Although CaMK IId is ubiquitously expressed, CaMK IIb shows preferential expression in neuroendocrine tissues. In comparison with the expression of a key regulatory enzyme in glucose oxidation, pyruvate dehydrogenase, two of the four CaM kinases investigated are expressed at equally high levels, which supports an important role in beta-cell physiology. These results provide the basis for exploring the pathophysiological relevance of CaMK IIb in human diabetes. [Diabetologia (2000) 43: 465±473]

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“…In endocrine pancreas ␤ cells, the predominant glucose-sensor has been definitively identified as glucokinase by knock out of the gene in mice (32,33), and the significance of the specific GLUT 2 expression in rodent ␤ cells is still disputed, especially as the amount of the GLUT 2 isoform seems to be very low in human ␤ cells (34,35). German (36) has shown that ␤ cells overexpressing GLUT 1 do not lose their ability to sense changes in glucose concentration within the physiological range and to respond by an appropriate stimulation of the insulin gene promoter.…”

Section: Discussionmentioning

confidence: 99%

Role of the GLUT 2 Glucose Transporter in the Response of the L-type Pyruvate Kinase Gene to Glucose in Liver-derived Cells

Antoine¹,

Lefrançois‐Martinez²,

Guillou³

et al. 1997

Journal of Biological Chemistry

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The expression of the L-PK gene in GLUT 2(؊) cells cultured in the absence of glucose was correlated with a high intracellular glucose 6-phosphate (Glu-6-P) concentration while under similar culture conditions Glu-6-P concentration was very low in GLUT 2(؉) cells. Consequently, a role of GLUT 2 in the glucose responsiveness of glucose-sensitive genes in cultured hepatoma cells could be to allow for Glu-6-P depletion under gluconeogenic culture conditions. In the absence of GLUT 2, glucose endogeneously produced might be unable to be exported from the cells and would be phosphorylated again to Glu-6-P by constitutively expressed hexokinase isoforms, continuously generating the glycolytic intermediates active on the L-PK gene transcription.

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Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression.

Cited by 359 publications

References 42 publications

Oscillatory control of insulin secretion

Oscillatory control of insulin secretion

Cloning and quantitative determination of the human Ca 2+ /calmodulin-dependent protein kinase II (CaMK II) isoforms in human beta cells

Role of the GLUT 2 Glucose Transporter in the Response of the L-type Pyruvate Kinase Gene to Glucose in Liver-derived Cells

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