Objectives: 

Nutritional deficiencies play an important role in the impairment of glucose homeostasis. This restricted condition leads to changes in pancreatic beta cell function and peripheral insulin actions. It's important to know, that glucose homeostasis also depends on glucagon effects. Therefore, we studied the alpha cell function and glucagon signalling in a low protein mice model compared with normal chow mice fed.

Materials: 

The experiments were performed with Swiss albino OF1 mice, distributed in a normal- diet (17% protein; NP) or a low-protein diet group (6% protein; LP). Both diets had identical calories. Calcium signals were analyzed by confocal microscopy, glucagon secretion by radioimmunoassay, gene expression by real-time PCR and protein levels by Western blot.

Results: 

We found that in LP mice calcium signalling and glucagon secretion were altered in pancreatic alpha cells. These changes were not related with alterations in glucagon gene expression or glucagon content. When we analyzed the alpha cell mass, we observed that it was significantly increased in LP mice. The hepatic function was impaired in malnourished animals; we found changes in the phosphorylation of Protein Kinase A and CREB, in response to fasting or exogenous glucagon in NP animals. However, these responses were reduced in the LP group. Additionally, the up-regulated gene expression in response to fasting, of the hepatic glucagon receptor as well as several key hepatic enzymes was also disrupted in LP compared with controls. Finally, the liver glycogen mobilization in response to fasting and the ability of exogenous glucagon to raise plasma glucose levels was lower in our LP model.

Conclusions: 

The low protein diet leads to several adaptations in pancreatic alpha cell functions and changes in glucagon hepatic signalling. Although these changes may be beneficial for the adaptation of mice to malnourished, they might be detrimental in conditions of excess of food consumption.