Biotin Regulation of Pancreatic Glucokinase and Insulin in Primary Cultured Rat Islets and in Biotin- Deficient Rats

Abstract

Biotin has been reported to affect glucose homeostasis; however, its role on pancreatic islets of Langerhans has not been assessed. In this report, we demonstrate that physiologic concentrations of biotin stimulate glucokinase activity in rat islets in culture. Using the branched DNA (bDNA) assay, a sensitive signal amplification technique, we detected relative increases in glucokinase mRNA levels of 41.5 +/- 13% and 81.3 +/- 19% at 12 and 24 h respectively in islets treated with [10(-6) M] biotin. Because glucokinase activity controls insulin secretion, we also investigated the effect of biotin on insulin release. Treatment with [10(-6) M] biotin for 24 h increased insulin secretion. We extended our studies by analyzing the effect of biotin deficiency on pancreatic islet glucokinase expression and activity, as well as insulin secretion. Our results show that islet glucokinase activity and mRNA are reduced by 50% in the biotin deficient rat. Insulin secretion in response to glucose was also impaired in islets isolated from the deficient rat. These data show that biotin affects pancreatic islet glucokinase activity and expression and insulin secretion in cultured islets.

Beta-Cell Function and Failure in Type 1 Diabetes

“…A positive effect of biotin on insulin secretion has been reported (RomeroNavarro, G. et al 1999;Sone, H. et al 2000;Sone, H. et al 1999;Vilches-Flores, A. et al 2009). Studies by our group (Romero-Navarro, G. et al 1999;Vilches-Flores, A. et al 2009) and others (Sone, H. et al 2000;Sone, H. et al 1999) have revealed that glucose-stimulated insulin secretion increases in response to acute exposure to pharmacological doses of biotin in either primary cultured islets (Romero-Navarro, G. et al 1999), perifused pancreas (Sone, H. et al 1999) or perifused islets (Sone, H. et al 2000). This effect of biotin on insulin secretion also appears to be dose-dependent (Sone, H. et al 1999).…”

“…We have found that biotin stimulates insulin and pancreatic glucokinase expression (Romero-Navarro, G. et al 1999), an enzyme that plays an important role in glucose homeostasis regulating insulin secretion in response to changes in blood glucose concentrations. Our group found that biotin concentrations of 10 to 1000 nM augmented glucokinase activity and mRNA abundance in cultured rat pancreatic islets (Romero-Navarro, G. et al 1999). A similar stimulatory effect on pancreatic glucokinase was observed in the insulinoma RIN 1046-38 cell line (Borboni, P. et al 1996).…”

Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process

“…In reference to the latter, biotin status has been shown to influence the expression of more than 2,000 human genes, at both the transcriptional and post-transcriptional levels (3, 30, 44). The affected genes include those that are critical for maintaining the differentiated phenotype of pancreatic beta cells, preservation of their mass (i.e., their proportion), and for insulin secretion (3,30,38,44). In reference to the latter, the vitamin has been shown to increases the expression of pancreatic and duodenal homeobox 1 (Pdx-1) (44), a critical transcription factor for the expression of insulin, and several genes involved in its synthesis and secretion by pancreatic beta cells (2).…”

“…24,29). In reference to the latter, biotin status has been shown to influence the expression of more than 2,000 human genes, at both the transcriptional and post-transcriptional levels (3,30,44). The affected genes include those that are critical for maintaining the differentiated phenotype of pancreatic beta cells, preservation of their mass (i.e., their proportion), and for insulin secretion (3,30,38,44).…”

“…In reference to the latter, the vitamin has been shown to increases the expression of pancreatic and duodenal homeobox 1 (Pdx-1) (44), a critical transcription factor for the expression of insulin, and several genes involved in its synthesis and secretion by pancreatic beta cells (2). In pancreatic beta cells, biotin appears to increase the expression of insulin receptor (7) and glucokinase (3,30,39), a rate-limiting enzyme in glucose-stimulated insulin secretion (20). It also decreases the expression of several gluconeogenic genes (6,36).…”