Specific and Combined Effects of Insulin and Glucose on Functional Pancreatic β-Cell Mass in Vivo in Adult Rats

Paris, Maryline; Bernard-Kargar, Catherine; Berthault, Marie‐France; Bouwens, Luc; Ktorza, Alain

doi:10.1210/en.2002-221112

Cited by 123 publications

(130 citation statements)

References 43 publications

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“…They found that a reduction of IR expression strongly inhibited insulin secretion and blocked mRNA expression of the glucose-regulated genes INS, insulin promoter factor 1 (IPF1) and glucokinase (GCK). Moreover, loss of Igf1r inhibited glucose-dependent insulin seretion, glucose-dependent ATP accumulation, but not expression of the aforementioned glucose-regulated genes [2]. Therefore, beta cells require function of both IR and Igf-IR for the complete process of glucose-dependent insulin secretion.…”

Section: Discussionmentioning

confidence: 96%

“…Glucose is a major factor for proliferation of pancreatic beta cells in vivo and in vitro [1,2]. However, the pathways and mechanisms behind glucose-dependent regulation of growth and replication of pancreatic islets are largely unknown [3].…”

Section: Introductionmentioning

confidence: 99%

“…Among potent beta cell growth factors are nutrients like glucose or peptides like insulin, IGF-I or IGF-II. Furthermore, in situations where proliferation of pancreatic beta cells has been induced by IGF-I or growth hormone, this was strongly glucose dependent [2,4,5]. Increased glucose concentrations of 10-20 mmol/l were found to inhibit apoptosis in single beta cell cultures, compared with lower glucose levels [6].…”

Section: Introductionmentioning

confidence: 99%

“…They are highly homologous in terms of amino acid sequence and structure and are in the IR family [2,5,7,8]. Almost certainly, these receptors form chimeric receptor hybrids of IGF-IR (αIRβIR,αIG FIRβIGFIR), IR-IRR (αIRβIR,αIRRβIRR) and IGF-IR-IRR (αIGFIRβIGFIR,αIRRβIRR) tetramers that depend on specific expression levels for each receptor type [9].…”

Section: Introductionmentioning

confidence: 99%

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Glucose concentration and AMP-dependent kinase activation regulate expression of insulin receptor family members in rat islets and INS-1E beta cells

et al. 2005

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Aims/hypothesis: Glucose and the peptide growth factors insulin, IGF-I and IGF-II strongly regulate beta cell mass. Furthermore, beta cell expression of IGF-I receptor (Igf1r) and insulin receptor (Insr) is mandatory for several steps of insulin secretion. Materials and methods: We hypothesised that glucose concentration might regulate expression of Igf1r, Insr and insulin receptor-related receptor (Insrr) in islets and beta cells. Moreover, since the ratio of ATP:ADP is the most important intracellular mechanism involved in insulin secretion, and since depletion of ATP leads to AMP accumulation, we evaluated the role of AMP-activated protein kinase (AMPK) in glucose-dependent receptor regulation. Results: In rat islets, high glucose exposure (25 mmol/l) increased gene expression of Igf1r, Insr and Insrr but also of the metabolic glycolysis gene liver-type pyruvate kinase (Pklr) compared with intermediate (6.2 mmol/l) or low glucose concentration (1.6 mmol/l) after 24 h. In rat INS-1E beta cells, only Pklr expression was suppressed by low glucose as in islets, while Insr and Insrr were suppressed by high and increased by low glucose levels. Igf1r expression was suppressed by both high-and low-glucose concentration. Activation of AMPK by 5-amino-imidazolecarboxamide riboside (AICAR, 0.5 mmol/l) suppressed Pklr expression, but strongly stimulated gene expression of Igf1r, Insr and Insrr. Protein expression of IR and IGF-IR reflected glucose and AICARregulated mRNA expression of both receptors in INS-1E cells. Conclusions/interpretation: We conclude that glucose directly interacts with islet and beta cell expression of growth factor receptors that are mandatory for both beta cell growth and insulin secretion. Stimulation of Igf1r and Insr gene expression by the AMPK-activator AICAR might indicate involvement of AMPK in the regulation of Igf1r, Insr and Insrr expression in beta cells.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glucose concentration and AMP-dependent kinase activation regulate expression of insulin receptor family members in rat islets and INS-1E beta cells

et al. 2005

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“…For example, in rats, glucose infusion increases beta cell numbers by 50% [81], with neogenesis of precursor cells being a dominant contributor to the increased mass [82]. Furthermore, glucose promotes beta cell survival by suppressing a constitutive apoptotic programme in vivo [83], and there is evidence that chronic changes in beta cell glucose metabolism induced by genetic or pharmacological manipulation of glucokinase can regulate beta cell mass regeneration in vivo [84].…”

Section: Contributors To Maintenance Of Islet Cell Mass In Adult Rodentsmentioning

confidence: 99%

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Mezza

Kulkarni

2014

Diabetologia

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Regeneration of mature cells that produce functional insulin represents a major focus and a challenge of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes, as well as in ageing. The capacity to adapt to diverse physiological states during life and the consequent ability to cope with increased metabolic demands in the normal regulation of glucose homeostasis is a distinctive feature of the endocrine pancreas in mammals. Both beta and alpha cells, and presumably other islet cells, are dynamically regulated via nutrient, neural and/or hormonal activation of growth factor signalling and the post-transcriptional modification of a variety of genes or via the microbiome to continually maintain a balance between regeneration (e.g. proliferation, neogenesis) and apoptosis. Here we review key regulators that determine islet cell mass at different ages in mammals. Understanding the chronobiology and the dynamics and agedependent processes that regulate the relationship between the different cell types in the overall maintenance of an optimally functional islet cell mass could provide important insights into planning therapeutic approaches to counter and/or prevent the development of diabetes.

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Polyamines regulate cell growth and cellular methylglyoxal in high‐glucose medium independently of intracellular glutathione

et al. 2016

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Edited by Miguel De la RosaPolyamines can presumably inhibit protein glycation, when associated with the methylglyoxal inevitably produced during glycolysis. Herein, we hypothesized a nonenzymatic interaction between putrescine and methylglyoxal in putrescine-deficient or -overexpressing Dictyostelium cells in high-glucose medium, which can control methylglyoxal production. Putrescine was essentially required for growth rescue accompanying methylglyoxal detoxification when cells underwent growth defect and cell cycle G1-arrest when supplemented with high glucose. Furthermore, methylglyoxal regulation by putrescine seemed to be a parallel pathway independent of the changes in cellular glutathione content in high-glucose medium. Consequently, we suggest that Dictyostelium cells need polyamines for normal growth and cellular methylglyoxal regulation.Keywords: Dictyostelium discoideum; glutathione; methylglyoxal; polyamines; putrescine High amounts of cellular glucose, a simple aldosic monosaccharide and a reducing sugar, can cause cellular damage that is followed by increased production of chemically reactive MG in mammals [1]. Glucose has been elucidated as a major a-dicarbonyl compound causing AGEs to form and furthermore is associated with engagement of their cellular RAGE in diabetic complications [2]. Particularly, MG has been strongly suggested to activate nonenzymatic glycation of proteins to form irreversible AGEs [3,4]. Although the biochemical origins of MG production have still not been addressed distinctly [5], MG seems to alter the intracellular content of both GSH and ROS in eukaryotes [6].To explain the biochemical roles of MG and its regulating enzymes, many types of enzyme systems have been proposed in mammals [7,8]. In microorganisms, our current study revealed that cellular MG levels altered Candida cell physiology and differentiation through their MG-consuming enzyme systems [9,10]. Additionally, we previously reported the crucial effect of MG on cell growth, cell cycle, and differentiation when MG-reducing aldose reductase (AlrA) is regulated in Dictyostelium [11]. However, nonenzymatic MG-scavenging molecules have not been sufficiently studied either in vitro or in vivo. The limited cellular MG regulation by MG-consuming enzymes is not sufficient for the nonenzymatic MG production,

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Specific and Combined Effects of Insulin and Glucose on Functional Pancreatic β-Cell Mass in Vivo in Adult Rats

Cited by 123 publications

References 43 publications

Glucose concentration and AMP-dependent kinase activation regulate expression of insulin receptor family members in rat islets and INS-1E beta cells

Glucose concentration and AMP-dependent kinase activation regulate expression of insulin receptor family members in rat islets and INS-1E beta cells

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Polyamines regulate cell growth and cellular methylglyoxal in high‐glucose medium independently of intracellular glutathione

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