Insulin Secretagogues, But Not Glucose, Stimulate an Increase in [Ca2+]i in the Fetal Rat β-cell

Weinhaus, Anthony J.; Poronnik, Philip; Cook, David I.; Tuch, Bernard E.

doi:10.2337/diab.44.1.118

Cited by 33 publications

(20 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the current study has confirmed previous data showing that glucose was unable significantly to stimulate release of insulin from control fetal islets (Weinhaus et al 1995, Tu & Tuch 1996. A possible explanation for this immaturity of function is an insufficient glucose oxidative phosphorylation in mitochondria with inadequate synthesis of ATP (Hughes 1994) and a failure to close ATP-dependent K + channels (Rorsman et al 1989).…”

Section: Tablesupporting

confidence: 79%

Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet

Cherif¹,

Reusens²,

Ahn³

et al. 1998

Journal of Endocrinology

148

115

View full text Add to dashboard Cite

An isocaloric low-protein (LP) diet (8% instead of 20% in controls) given to dams during gestation reduces the fractional insulin release of stimulated fetal islets. The LP diet lowers the plasma concentration of taurine in both pregnant rats and their fetuses. This study reports the effect of taurine on the in vitro release of insulin from control and LP fetal islets. Direct stimulation with taurine, methionine or leucine increased the release of insulin from control islets. Nevertheless, no effect on LP islets was observed with either taurine or methionine. The release of insulin from LP islets was reduced with leucine. The in vitro addition of taurine (0·3 or 3 mM) to the culture medium increased the release of insulin from the control islets in response to arginine or leucine, but it did not restore the reduced responsiveness of LP islets to these amino acids. When 2·5% taurine was added to the drinking water of control or LP dams (groups C+T and LP+T) throughout gestation, the concentration of taurine increased in the serum of dams and fetuses of both groups. The release of insulin from the LP+T fetuses was restored to control levels when stimulated with taurine, methionine, leucine or arginine. In conclusion, taurine stimulated control fetal islets in vitro, but failed to do so in LP islets. However, the addition of taurine to the diet of LP dams restored to normal the release of insulin from LP fetal islets, indicating the importance of taurine during development for a normal fetal cell function.

show abstract

Section: Tablesupporting

confidence: 79%

Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet

Cherif¹,

Reusens²,

Ahn³

et al. 1998

Journal of Endocrinology

148

115

View full text Add to dashboard Cite

show abstract

“…Arginine is known to stimulate insulin secretion by the mechanisms that are different from those used by glucose, although the detail remains controversial (50,51). However, it seems certain that arginine somehow evoked Ca 2ϩ influx into the ␤ cell, and that leads to the exocytosis of insulincontaining vesicles (52,53). So at least, the decreased insulin secretion in RIP-G Tg might not be due to disorders in exocytosis process.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Rat Insulin II Promoter-Ghrelin Transgenic Mice and Rat Glucagon Promoter-Ghrelin Transgenic Mice

Iwakura¹,

Hosoda²,

Son³

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

We developed and analyzed two types of transgenic mice: rat insulin II promoter-ghrelin transgenic (RIP-G Tg) and rat glucagon promoter-ghrelin transgenic mice (RGP-G Tg). The pancreatic tissue ghrelin concentration measured by C-terminal radioimmunoassay (RIA) and plasma desacyl ghrelin concentration of RIP-G Tg were about 1000 and 3.4 times higher than those of nontransgenic littermates, respectively. The pancreatic tissue n-octanoylated ghrelin concentration measured by N-terminal RIA and plasma n-octanoylated ghrelin concentration of RIP-G Tg were not distinguishable from those of nontransgenic littermates. RIP-G Tg showed suppression of glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion, pancreatic insulin mRNA and peptide levels, ␤ cell mass, islet architecture, and GLUT2 and PDX-1 immunoreactivity in RIP-G Tg pancreas were not significantly different from those of nontransgenic littermates. Islet batch incubation study did not show suppression of insulin secretion of RIP-G Tg in vitro. The insulin tolerance test showed lower tendency of blood glucose levels in RIP-G Tg. Taking lower tendency of triglyceride level of RIP-G Tg into consideration, these results may indicate that the suppression of insulin secretion is likely due to the effect of desacyl ghrelin on insulin sensitivity. RGP-G Tg, in which the pancreatic tissue ghrelin concentration measured by C-RIA was about 50 times higher than that of nontransgenic littermates, showed no significant changes in insulin secretion, glucose metabolism, islet mass, and islet architecture. The present study raises the possibility that desacyl ghrelin may have influence on glucose metabolism.Ghrelin is a 28-amino acid peptide with unique modification of acylation, which is essential for its biological action (1). Ghrelin was originally identified in rat stomach as an endogenous ligand for an orphan receptor, which has been so far called growth hormone secretagogue receptor (GHS-R) 1 (1). Ghrelin expression is detected in the stomach, intestine, hypothalamus, pituitary gland, kidney, placenta, and testis (2-6). Ghrelin is involved in a wide variety of the functions, including the regulation of growth hormone release, food intake, gastric acid secretion, gastric motility, blood pressure, and cardiac output (7-19).Recently Date et al. (20) reported that ghrelin is present in ␣ cells of normal human and rat pancreatic islets. Volante et al. (20,31,32). Salehi et al. have reported ghrelin has both inhibitory and stimulatory effects depending on its concentration (33). Therefore, there is still a lot of controversy about the localization of ghrelin in the pancreas and the effects of ghrelin on the insulin secretion. As for the effects of desacyl ghrelin on insulin secretion, Broglio et al. (34) have reported that acute desacyl ghrelin administration has no effect on insulin secretion in human but that it counteracts the inhibitory effect of n-octanoylated ghrelin on insulin secretion when co-administrated with n-octanoylated ghrelin (35).Here...

show abstract

“…1 The abbreviations used are: GK, glucokinase; NIDDM, non-insulindependent diabetes mellitus; ES cell, embryonic stem cell; HK, hexokinase; Hanks'-BSA buffer, Hanks'-buffered saline containing 0.2% bovine serum albumin. ments of intracellular calcium concentration were carried out using fura-2 acetoxymethylester (Molecular Probes) (19,20) by the method of Weinhaus et al (20).…”

Section: Methodsmentioning

confidence: 99%

“…A rise in the intracellular Ca 2ϩ concentration in the ␤-cell ([Ca 2ϩ ] i ) is a key event in glucose-stimulated insulin secretion (19,20). Although all the GK-deficient islets looked alike under microscopy, they could be subdivided into two groups in terms of basal [Ca 2ϩ ] i levels; those with normal calcium levels (110 Ϯ 34 nM, n ϭ 7; about 20% of the islets), and those with higher basal calcium levels (higher than 200 nM; about 80%) which might reflect some damage of the islets.…”

Section: Diabetes Mellitus In Mice Lacking ␤-Cell Glucokinase 30254mentioning

confidence: 99%

Pancreatic β-Cell-specific Targeted Disruption of Glucokinase Gene

Terauchi

Sakura

Yasuda

et al. 1995

Journal of Biological Chemistry

223

View full text Add to dashboard Cite

Mice carrying a null mutation in the glucokinase (GK) gene in pancreatic ␤-cells, but not in the liver, were generated by disrupting the ␤-cell-specific exon. Heterozygous mutant mice showed early-onset mild diabetes due to impaired insulin-secretory response to glucose. Homozygotes showed severe diabetes shortly after birth and died within a week. GK-deficient islets isolated from homozygotes showed defective insulin secretion in response to glucose, while they responded to other secretagogues: almost normally to arginine and to some extent to sulfonylureas. These data provide the first direct proof that GK serves as a glucose sensor molecule for insulin secretion and plays a pivotal role in glucose homeostasis. GK-deficient mice serve as an animal model of the insulin-secretory defect in human noninsulin-dependent diabetes mellitus.Glucokinase (GK), 1 mainly expressed in pancreatic ␤-cells and the liver, is thought to constitute a rate-limiting step in glucose metabolism in these tissues (1-4). Since insulin secretion parallels glucose metabolism and the high K m of GK (5-8 mM) ensures that it can change its enzymatic activity within the physiological range of glucose concentrations, GK has been proposed to act as a glucose sensor in the pancreatic ␤-cell (1, 5). Recently, mutations of the GK gene have been identified in patients with maturity-onset diabetes of the young, a subtype of early-onset non-insulin-dependent diabetes mellitus (NIDDM) (6 -8). However, since all the mutations in humans so far occur in the region of the gene that is common to pancreatic ␤-cells and hepatocytes (9), and are heterozygous, it may not have been possible to fully reveal physiological roles of pancreatic ␤-cell GK either in vivo or in vitro. To this end, mice carrying a null mutation in the GK gene in pancreatic ␤-cells, but not in the liver, were generated by homologous recombination. Heterozygous mutant mice showed early-onset mild diabetes resembling the phenotype for human maturity-onset diabetes of the young. Homozygotes showed severe diabetes shortly after birth and died within a week. GK-deficient islets showed defective insulin secretion in response to glucose, while they responded to other secretagogues: almost normally to arginine and to some extent to sulfonylureas. These data provide the first direct proof that GK serves as a glucose sensor molecule for insulin secretion and plays a pivotal role in glucose homeostasis. EXPERIMENTAL PROCEDURESCloning of the Mouse GK Gene, Construction of a Targeting Vector, and Homologous Recombinant Experiments-A DNA fragment including the pancreatic ␤-cell-specific exon 1␤ of the GK gene was cloned from a BALB/c mouse genomic library (Clontech). A BamHI site was introduced 30 base pairs 3Ј to the translation initiation codon of GK by the Kunkel method (10). A neomycin resistance gene (neo r ) with a pgk-1 promoter but without a poly(A) ϩ addition signal was substituted for the XbaI-BamHI fragment in the exon 1␤. A diphtheria toxin A fragment gene (DTA) with a MC1 promoter was lig...

show abstract

Insulin Secretagogues, But Not Glucose, Stimulate an Increase in [Ca2+]i in the Fetal Rat β-cell

Cited by 33 publications

References 32 publications

Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet

Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet

Analysis of Rat Insulin II Promoter-Ghrelin Transgenic Mice and Rat Glucagon Promoter-Ghrelin Transgenic Mice

Pancreatic β-Cell-specific Targeted Disruption of Glucokinase Gene

Contact Info

Product

Resources

About