Type 1 diabetic patients develop severe secondary complications because insulin treatment does not guarantee normoglycemia. Thus, efficient regulation of glucose homeostasis is a major challenge in diabetes therapy. Skeletal muscle is the most important tissue for glucose disposal after a meal. However, the lack of insulin during diabetes impairs glucose uptake. To increase glucose removal from...

Bacillus sphaericus cannot metabolize sugar since it lacks several of the enzymes necessary for glycolysis. Our results confirmed the presence of a glucokinase-encoding gene, glcK, and a phosphofructokinase-encoding gene, pfk, on the bacterial chromosome and expression of glucokinase during vegetative growth of B. sphaericus strains. However, no phosphoglucose isomerase gene (pgi) or phosphoglu...

The purposes of these studies were (a) to examine the kinetics of glucose uptake by isolated perfused livers over a wide range of glucose concentrations (i.e. 2 to 80 mu), and (6) to compare observed rates of net hepatic glucose uptake and hepatic glucose phosphorylation calculated therefrom with levels of the liver glucose-phosphorylating enzymes glucokinase and hexokinase which were measured ...

Glucokinase is one of the four hexokinases present in mammalian tissues. It is expressed in two cell types that have to respond to changes in the blood glucose concentration, the liver parenchymal cell and the /3-cells of pancreatic islets. The former are responsible for the metabolism and storage of an important part of the ingested glucose, whereas the latter secrete insulin in response to an...

Diabetes is associated with severe secondary complications, largely caused by poor glycemic control. Treatment with exogenous insulin fails to prevent these complications completely, leading to significant morbidity and mortality. We previously demonstrated that it is possible to generate a "glucose sensor" in skeletal muscle through coexpression of glucokinase and insulin, increasing glucose u...

Glucokinase regulates insulin secretion by controlling the rate of glucose phosphorylation. In this report we utilize islets transgenic for high affinity yeast hexokinase to examine the role of glucose phosphorylation on other beta cell functions. Normal pancreatic islets responded to culture in low glucose by lowering insulin synthetic rates, becoming depleted of insulin and insulin mRNA, losi...

The cause of compensatory hyperinsulinemia in normoglycemic insulin-resistant states is unknown. Using spontaneously hypertensive rats (SHR), we tested the hypothesis that a lowered beta-cell set-point for glucose causes a hypersecretion of insulin at a normal glucose level. Islets isolated from normoglycemic hyperinsulinemic SHR were compared to age-matched (12 wk old) Wistar-Kyoto (WK) rats. ...

To identify the amino acids involved in the specific regulatory properties of glucokinase, and particularly its low affinity for glucose, mutants of the human islet enzyme have been prepared, in which glucokinase-specific residues have been replaced. Two mutations increased the affinity for glucose by twofold (K296M) and sixfold (Y214A), the latter also decreasing the Hill coefficient from 1.75...