Effects of non-glycated and glycated glucagon-like peptide-1(7-36) amide on glucose metabolism in isolated mouse abdominal muscle.

This study investigated the actions of non-glycated and glycated glucagon-like peptide-1(7-36)amide (tGLP-1) on glucose uptake and metabolism in isolated mouse abdominal muscle. Monoglycated tGLP-1 (Mr 3463.8) was prepared under hyperglycemic reducing conditions and purified by HPLC.

Antihyperglycaemic effect of saccharin in diabetic ob/ob mice.

1. The effect of chronic saccharin (benzosulphimide) consumption on glucose homeostasis was examined in normal lean +/+ mice and genetically obese hyperglycaemic insulin-resistant ob/ob mice. 2.

Characterization of insulin glycation in insulin-secreting cells maintained in tissue culture.

Characteristics of cellular insulin glycation were examined in the pancreatic B-cell line, BRIN-BD11. The extent of insulin glycation increased stepwise during 72 h of culture at 5.6-33.

Effect of vitamin C supplementation on hepatic cytochrome P450 mixed-function oxidase activity in streptozotocin-diabetic rats.

The effect of vitamin C supplementation on hepatic cytochrome P450 expression was investigated in streptozotocin (STZ) diabetic male Wistar Albino rats. STZ-treated rats displayed the usual characteristics of diabetes including; hyperphagia, polydipsia, decreased body weight gain and also the increased expression and activity of hepatic CYP1A, 2B, 2E and 4A proteins. Vitamin C administration in drinking water (2% w/v) was associated with significant decreases in the levels of hyperglycaemia (P < 0.

Mechanisms of amino acid-induced insulin secretion from the glucose-responsive BRIN-BD11 pancreatic B-cell line.

The effects of different classes of amino acids known to be transported and utilized by pancreatic B-cells were examined using the novel glucose-responsive pancreatic B-cell line, BRIN-BD11. Amino acids tested included alpha-aminoisobutyric acid, L-alanine, L-arginine, L-glutamine, glycine, L-leucine, L-lysine, L-proline and L-serine. At non-stimulatory (1.

Glycation of insulin in the islets of Langerhans of normal and diabetic animals.

The glycation of immunoreactive insulin (IRI) was assessed in extracts of pancreas and islets from control and hyperglycemic animal models. Glycated and nonglycated IRI were separated by affinity chromatography and quantified by radioimmunoassay. Hydrocortisone-treated Wistar rats (80 mg x kg-1 x day-1 and obese hyperglycemic (ob/ob) mice showed significant increases in plasma glucose (P < 0.

Characterization of a novel glucose-responsive insulin-secreting cell line, BRIN-BD11, produced by electrofusion.

A novel insulin-secreting cell line (BRIN-BD11) was established after electrofusion of RINm5F cells with New England Deaconess Hospital rat pancreatic islet cells. Wells of cell fusion mixture with insulin output 5-10 times greater than parent RINm5F cells were subcultured with eventual establishment of clones, including BRIN-BD11. Morphological studies established that these cells grow as monolayers with epithelioid characteristics, maintaining stability in tissue culture for > 50 passages.

Hexose recognition by insulin-secreting BRIN-BD11 cells.

Clonal BRIN-BD11 cells were produced by electrofusion of NEDH rat islet B-cells with immortal RINm5F cells. Western blotting analysis revealed that unlike RINm5F, novel BRIN-BD11 cells expressed high levels of the glucose transport protein GLUT-2, coupled with a rapid and sustained uptake of D-glucose, significantly greater than RINm5F after only 5 min (p < 0.05).

D-glucose metabolism in BRIN-BD11 islet cells.

A novel insulin-secreting cell line, BRIN-BD11, was recently established following electrofusion of RINm5F cells with NEDH rat pancreatic islet cells. In the present study, D-glucose metabolism was compared in BRIN-BD11 and RINm5F cells. The concentration dependency of D[5-3H]glucose utilization displayed a comparable pattern in the two cell lines, but the absolute values were lower in BRIN-BD11 than RINm5F cells.

Characteristics of BRIN-BG5 and BRIN-BG7, two novel glucose-responsive insulin-secreting cell lines produced by electrofusion.

Two hybrid insulin-secreting cell lines (BRIN-BG5 and BRIN-BG7) were established by the novel approach of electrofusing RINm5F cells with New England Deaconess Hospital rat pancreatic islet cells. Cells were selected from the fusion mixture on the basis of insulin output. Wells showing five to ten times greater insulin output than parental RINm5F cells were selected, subcultured and cloned.

PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells.

Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic beta cells. The molecular mechanisms involved are not fully understood but are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (KATP channels) in the beta cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machinery not involving closure of the plasma membrane KATP channels.

Identification of the site of glycation of human insulin.

This study evaluates the nature of glycated human insulin formed following exposure to hyperglycemic conditions in vitro. Glycated insulin was purified by RP-HPLC and its molecular mass (5971.3 Da) determined by plasma desorption mass spectrometry (MS).

Defective expression of cytochrome P450 proteins in the liver of the genetically obese Zucker rat.

The hepatic expression of xenobiotic-metabolising cytochrome P450 isoforms in the genetically obese Zucker rat, a model of obesity, was compared to that of its lean littermate. Cytochrome P450 (CYP) levels were determined using diagnostic substrates and/or immunologically in Western blot analyses. When compared with the lean Zucker rat, the obese animal exhibited hyperglycaemia, hypercholesterolaemia, marked hyperinsulinaemia and hypertriglyceridaemia but was normoketonaemic.

Modulation of the rat hepatic cytochrome P450 composition by long-term streptozotocin-induced insulin-dependent diabetes.

The effects of long-term insulin-dependent diabetes on the enzymatic activities of hepatic cytochrome P450 isozymes were determined in rats rendered diabetic by the administration of streptozotocin and killed 4, 8, and 12 weeks following treatment. The O-dealkylations of ethoxyresorufin and pentoxyresorufin were elevated in the diabetic animals throughout the study, the extent of increase being similar at all three time points. p-Nitrophenol hydroxylase activity was induced in the diabetic animals 4 weeks following treatment with streptozotocin, but the extent of increase became less pronounced with the progress of the disease.

New perspectives on the actions of sulphonylureas and hyperglycaemic sulphonamides on the pancreatic beta-cell.

Sulphonylureas and the hyperglycaemic sulphonamide diazoxide are commonly employed in the therapy of non-insulin-dependent (Type 2) diabetes mellitus and insulinoma, respectively. Stimulatory effects of sulphonylureas on insulin secretion and the inhibitory action of diazoxide are thought to be primarily mediated through modulation of the activity of ATP-sensitive K+ channels (K(+)-ATP channels) in the beta-cell plasma membrane. Certain sulphonylureas are known to be internalised by the pancreatic B-cell.

Effects of copper deficiency and experimental diabetes on tissue antioxidant enzyme levels in rats.

Male weanling rats were fed diets containing either adequate (6.2 mg/kg) or deficient (0.82 mg/kg) quantities of copper for 35 days.

Sex differences in the diabetes-induced modulation of rat hepatic cytochrome P450 proteins.

Sex differences in the diabetes-induced changes in hepatic cytochrome P450 proteins were investigated in rats treated with streptozotocin. Changes in specific cytochrome P450 proteins were monitored using diagnostic substrates and immunologically utilizing specific polyclonal antibodies. When expressed in terms of nmoles of total cytochrome P450, ethoxyresorufin O-deethylase activity was increased by treatment with streptozotocin, the extent of induction being the same in the two sexes.

Induction of rat hepatic mixed-function oxidases by acetone and other physiological ketones: their role in diabetes-induced changes in cytochrome P450 proteins.

1. To evaluate the role of ketone bodies in diabetes-induced changes in hepatic cytochrome P450 composition, rats were treated with acetone, 3-hydroxybutyrate or 1,3-butanediol. 2.