The glucose-induced synthesis of insulin in liver

Abstract

Pancreatic β cells, stimulated by glucose, are known to synthesize and secrete insulin. As liver diseases are reported to cause diabetes mellitus, studies were conducted to determine the possibility of glucose-induced insulin synthesis in the liver cells. The glucose-induced insulin synthesis was determined by in vitro translation of mRNA from the hepatocytes. The cDNA from mRNA was prepared and sequence analysis was performed. Incubation of hepatocytes from the liver of adult mice (n=10) with glucose (0.02 M) resulted in the insulin synthesis [0.03 (mean)±0.006 (S.D.) μunits/mg/h] compared to the pancreatic β cells [0.04±0.004 μunits/mg/h]. Immunohistochemical study also demonstrated the glucose-induced synthesis of insulin in liver cells. Incubation of the mice hepatocytes with glucose resulted in the synthesis of insulin mRNA. The purified mRNA which was used to prepare cDNA resulted in the formation of proinsulin I and proinsulin II genes corresponding to 182 and 188 base pairs, respectively. Sequence analysis of the cDNA indicated that proinsulin I as well as proinsulin II gene could be involved in the synthesis of insulin by hepatocytes. These results suggested that insulin synthesis in both hepatic and pancreatic cells could be involved in the control of diabetes mellitus.

The Control of Hyperglycemia in Alloxan Treated Diabetic Mice through the Stimulation of Hepatic Insulin Synthesis due to the Production of Nitric Oxide

“…Hepatocytes from adult mice were prepared in 10 mM HEPES solution (pH 7.4) without glucose at 4 °C ( Ghosh et al, 2010 ;Guillam et al, 1998 ).…”

The Activation by Glucose of Liver Membrane Nitric Oxide Synthase in the Synthesis and Translocation of Glucose transporter-4 in the Production of Insulin in the Mice Hepatocytes

“…We, on the other hand, have recently reported that a glucose dependent synthesis and secretion of insulin also occurred in the hepatocytes in adult mice [3]. It should be mentioned here that various etiological and demographical studies have previously suggested that the liver could have a significant contribution in both the long and short term of glucose homeostasis [4], and the chronic hepatitis is reported to lead to diabetes mellitus [5].…”

“…The role of glucose induced NO production both in the liver membrane translocation of Glut-4 as well as in the synthesis of Glut-4 in the hepatic cells for the expression of the genetic elements leading to the synthesis of insulin by the sugar in the liver were investigated [3]. …”

Neutralization by Insulin of the Hypertensive Effect of Dermcidin Isoform 2: An Environmentally Induced Diabetogenic and Hypertensive Protein

“…We have reported before that dermcidin was capable of inducing T1BDM like condition due to the inhibition of glucose uptake both in the pancreatic islets of Langerhans and in the hepatocytes of the liver of adult mice [6]. As a consequence of the impaired glucose uptake in both kinds of cells, the sugar-induced synthesis of insulin was inhibited due to the impaired expression of both the proinsulin genes I and II in these cells [8, 27]. The human dermcidin was reported to be a potent inhibitor of all known forms of nitric oxide synthase (NOS) due to its ability to act as a competitive inhibitor of l -arginine, the only known substrate for all NOS [7].…”