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R A Reimer

Publications and source records attributed to R A Reimer.

6 recordsLinked to original sources
PubMed2001

A human cellular model for studying the regulation of glucagon-like peptide-1 secretion.

GLP-1 (glucagon-like peptide-1) is a potent insulin secretagogue released from L cells in the intestine. The regulation of GLP-1 secretion has been described both in vivo and in vitro in several animal species, but data from human cellular models are lacking. For this purpose, factors and cell-signaling pathways regulating GLP-1 secretion were investigated in the NCI-H716 human intestinal cell line. After differentiation, these cells homogeneously produced 16.8 pmol GLP-1/mg protein with a basal release of 4.2% during a 2-h incubation period. Nutrients, such as palmitic acid, oleic acid, and meat hydrolysate, stimulated GLP-1 secretion in a dose-dependent manner, as did the cholinergic agonist carbachol and the neuromediator gastrin-releasing peptide. Along with stimulating GLP-1 release, gastrin-releasing peptide, like ionomycin, increased intracellular calcium levels. Activators of PKA and PKC were able to increase GLP-1 secretion in NCI-H716 cells. However, neither PKA activators nor meat hydrolysate increased proglucagon mRNA levels. These findings indicate that the NCI-H716 cell line constitutes a unique model to study the cellular mechanism of GLP-1 secretion in humans and suggest potential interspecies divergence in the regulation of proglucagon gene expression in enteroendocrine cells.

Animals↗
PubMed1998

Proglucagon and glucose transporter mRNA is altered by diet and disease susceptibility in 30-day-old biobreeding (BB) diabetes-prone and normal rats.

Diet is an important factor influencing the development of diabetes in the Biobreeding (BB) rat. Changes in gut development and absorption of nutrients in the diabetes-prone rat (Bbdp) and the subsequent effect on pancreatic function may play a role in the ultimate development of the disease. BBdp and normal (BBn) dams were fed one of three diets, chow or semipurified diets containing either soy or casein as the protein source. Pups were weaned at 21 d onto the same diet as their respective dam and killed at 30 d. Chow-fed BBn animals weighed significantly more than casein- or soy-fed BBn animals. Chow-fed BBdp had significantly greater small intestine and colon weight when expressed on a per body weight basis than BBn. With all three diets, BBdp animals had significantly lower colonic proglucagon mRNA abundance than did BBn animals. Adjusting for total colonic RNA content resulted in only casein- and soy-fed BBdp animals demonstrating significantly lower colonic proglucagon mRNA abundance than did BBn animals. BBn animals had higher levels of sodium-dependent D-glucose cotransporter (SGLT)-1 and sodium-independent glucose transporter (GLUT) 5 mRNA than did BBdp. Within BBn animals, casein and soy produced significantly lower levels of SGLT-1 and GLUT5 mRNA than did chow. This study demonstrates that BBn and BBdp animals respond differently to chow versus semipurified weaning diets. These differences may explain the differences in growth and intestinal development among the BBdp and BBn strains weaned onto different diets.

Animals↗
PubMed1997

Ontogenic changes in proglucagon mRNA in BB diabetes prone and normal rats weaned onto a chow diet.

Weaning onto chow diets causes the highest incidence of diabetes in the BB rat. Changes in gut development and absorption of nutrients in the diabetes prone rat and the subsequent effect on pancreatic function may play a role in the ultimate development of the disease. BB diabetes prone (dp) and BB normal (n) dams were fed chow diets. Pups were killed at various ages ranging from 7 to 30 days. BBdp rats had higher small intestine and colon weights expressed per body weight at all ages (p < 0.0001). RNA content (mg/g) in the jejunum, ileum and colon was higher in the BBdp rats beginning at the critical period at 21 days and maintained at 24 days and 30 days (p < 0.0001). Proglucagon message decreased with age in both BBdp and BBn animals (p < 0.0001). Levels of proglucagon mRNA were higher in BBdp compared to BBn animals only in the ileum at 10 days (p < 0.01). Adjusting for total ileal and colonic RNA content resulted in BBdp animals having higher total colonic proglucagon mRNA at 21, 24 and 30 days (p < 0.0001). Plasma GLP-1(7-36) amide was more than doubled in BBdp compared to BBn animals (p < 0.0005) at 30 days. Expressing sodium-dependent D-glucose co-transporter (SGLT-1), GLUT2 and GLUT5 mRNA per total jejunal RNA shows increased transporter mRNA in BBdp compared to BBn rats at weaning (21 days) (p < 0.05). Radical differences exist between BBdp and BBn animals at 'critical periods' in both proglucagon and glucose transporter gene expression. These differences may help explain altered growth and diseases incidence between these two strains.

Age Factors↗
PubMed1997

A physiological level of rhubarb fiber increases proglucagon gene expression and modulates intestinal glucose uptake in rats.

Previous work demonstrated that a high fiber diet upregulates proglucagon mRNA and secretion of glucagon-like peptide-1 [GLP-1(7-37)] and insulin compared with an elemental fiber-free diet. This study examined whether similar intakes of fibers differing in physiochemical and fermentative properties alter the expression of intestinal hormones and intestinal absorptive properties. Sprague-Dawley rats were fed either a 50 g/kg cellulose or rhubarb fiber diet for 14 d. Ileal proglucagon mRNA levels were significantly higher in rats fed rhubarb fiber than in those fed cellulose fiber (9.3 +/- 0.9 vs. 6.2 +/- 1.0 densitometer units). Proglucagon mRNA in the colon did not differ between diet treatments. Plasma c-peptide concentrations were significantly higher 30 min after an oral glucose tolerance test in the rhubarb vs. cellulose group (1627 +/- 67 vs. 1290 +/- 71 pmol/L). Passive permeability, measured by the uptake of L-glucose, was significantly higher in the jejunum of rats fed cellulose compared with those fed rhubarb fiber. Adjusting total glucose uptake for passive permeability and unstirred water layer resistance resulted in a higher Km being calculated for the jejunum and ileum of the cellulose fiber group. Jejunal and ileal carrier-mediated uptakes (Vmax) were not altered by diet and reflected the lack of difference between groups in sodium-dependent glucose cotransporter (SGLT-1) and sodium-independent glucose transporter (GLUT2) mRNA levels. Replacing cellulose fiber with rhubarb fiber in a diet upregulated ileal proglucagon mRNA and resulted in a reduced passive permeability but did not affect glucose transport of the small intestine. This work establishes the importance of dietary fiber fermentability in modulating intestinal proglucagon expression and possibly glucose homeostasis.

Animals↗
PubMed1996

Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and postprandial secretion of glucagon-like peptide-1 and insulin in rats.

Intestinal hormones stimulate more than 50% of the insulin response after oral glucose administration. Short chain fatty acids stimulate mucosal adaptation and may alter proglucagon messenger RNA and release of the insulin secretagogue, glucagon-like peptide-1 (GLP-1). Sprague-Dawley rats ingested a fiber-free elemetnal diet or an elemental diet supplemented with 30% fiber providing similar energy and nutrients for 14 days. The cecal and colonic short chain fatty acids contents were significantly higher in the 30% fiber group. Ileal proglucagon messenger RNA levels were significantly higher in the 30% group vs. the 0% group (11.47 +/- 0.87 vs. 6.52 +/- 0.87 densitometer units), respectively. Similar trends were seen in the colon (13.36 +/- 1.0 vs. 10.90 +/- 0.77 densitometer units; P = 0.07). Plasma GLP-1, insulin, and C peptide levels 30 min postoral glucose were significantly higher in the 30% fiber group vs. the 0% group (19.8 +/- 1.2 vs. 15.4 +/- 1.2 pg/ml, 2.67 +/- 0.4 vs. 1.29 +/- 0.5 ng/ml, and 964.4 +/- 94.4 vs. 530.2 +/- 120.4 pM, respectively). Plasma glucose and glucagon did not differ between groups. A diet supplemented with fiber is able to significantly alter proglucagon gene expression and modulate GLP-1 and insulin secretion. These novel findings deepen our understanding of the beneficial role of fiber in improving glucose homeostasis.

Animals↗