Cluster analysis of rat pancreatic islet gene mRNA levels after culture in low-, intermediate- and high-glucose concentrations

Abstract

Aims/hypothesis Survival and function of insulin-secreting pancreatic beta cells are markedly altered by changes in nutrient availability. In vitro, culture in 10 rather than 2 mmol/l glucose improves rodent beta cell survival and function, whereas glucose concentrations above 10 mmol/l are deleterious.

Quantitative proteomic analysis of single pancreatic islets

“…Many regulated proteins have previously been associated with hyperglycemia in animal models for diabetes or in patients (Table S4). Concordant with a recently published microarray study (18) we find a general up-regulation of glycolysis, the TCA cycle and ATP translocation (Fig. 4).…”

“…Furthermore, we observed depletion of all three members of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) complex, which has also been correlated with insulin secretion deficiencies in diabetic animal models (31). In contrast, mRNA levels of SERCA increase after 18 h of glucose stimulation (18), possibly pointing to a compensatory mechanism for acute protein depletion. Vesicle access to the plasma membrane is thought to be hindered by dense cortical F-actin and depolymerization of F-actin upon glucose stimulation potentiates insulin secretion (32).…”

Control of Insulin Secretion by Cytochrome c and Calcium Signaling in Islets with Impaired Metabolism

“…Responses to KIC were nearly identical in islets cultured at 3 or 11 mM glucose (Fig. 3, A and B); consistent with the decrease in oxidative response to glucose, Ca 2ϩ increment was less in the 3 mM glucose culture islets, but only by about 20% (similar to results obtained by Jonas and co-workers (20), although our data did not achieve statistical significance). Results were also calculated after converting the fluorescence ratios to Ca 2ϩ concentrations using equations provided by (33), but the results differed by only a few percentage points.…”

“…To do this, two islet models with impaired metabolic response were used. The first model was induced by culturing islets in the presence of low glucose, which causes the loss of glucokinase (GK) activity, thereby decreasing the metabolic response to glucose (19,20). The second model of impaired metabolism was generated by fasting rats prior to islet isolation (21).…”

Glucokinase activation is beneficial or toxic to cultured rat pancreatic islets depending on the prevailing glucose concentration

“…apoptosis; glucotoxicity; insulin secretion; pancreatic ␤-cell GLUCOSE STIMULATION OF INSULIN SECRETION (GSIS) by endocrine pancreatic ␤-cells depends on the acceleration of glucose metabolism through glycolysis and the TCA cycle, with enhanced production of metabolic coupling factors (25,39,41). Besides these rapid effects, glucose exerts complex long-term effects on the ␤-cell phenotype (2,10,16,18,27,45). During long-term culture of rodent islets, ␤-cell gene expression, survival, and glucose responsiveness are optimally preserved in the presence of 10 mM glucose (G10), whereas they are markedly altered by culture at either nonstimulating (G5) or very high (G30) glucose concentrations.…”