Abstract
This study investigated the role of GABA in attenuating liver insulin resistance (IR) in type 2 diabetes parents and reducing its risk in their descendants’ liver. Both sexes’ rats were divided into four groups of non-diabetic control, diabetic control (DC), GABA-treated (GABA), and insulin-treated (Ins). The study duration lasted for six months and the young animals followed for four months. Consequently, hyperinsulinemic-euglycemic clamp was performed for all animals. Apart from insulin tolerance test (ITT), serum and liver lipid profile were measured in all groups. Glycogen levels, expression of Foxo1, Irs2, Akt2, and Pepck genes in the liver were assessed for all groups. Overall, GABA improved ITT, increased liver glycogen levels and decreased lipid profile, blood glucose level, and HbA1c in parents and their offspring in compared to the DC group. GIR also increased in both parents and their offspring by GABA. Moreover, the expression of Foxo1, Irs2, Akt2, and Pepck genes improved in GABA-treated parents and their descendants in compared to DC group. Results indicated that GABA reduced liver IR in both parents and their offspring via affecting their liver insulin signaling and gluconeogenesis pathways.
Highlights
This study investigated the role of GABA in attenuating liver insulin resistance (IR) in type 2 diabetes parents and reducing its risk in their descendants’ liver
Our results showed that area under the curve (AUC) in insulin tolerance test (ITT) significantly decreased in GABA or Ins groups compared with diabetic control (DC) group in both genders as much as the control group;
In the third months after birth, a significant decrease in AUC was observed in the female offspring of Ins and GABA group compared with the female offspring of non-diabetic control (NDC) group (P < 0.001, Fig. 2c–z)
Summary
This study investigated the role of GABA in attenuating liver insulin resistance (IR) in type 2 diabetes parents and reducing its risk in their descendants’ liver. GABA improved ITT, increased liver glycogen levels and decreased lipid profile, blood glucose level, and HbA1c in parents and their offspring in compared to the DC group. Among many of the molecules involved in the intracellular insulin signal processing in the liver, the genes protein kinase B (PKB, known as Akt2)[7], insulin receptor substrate 2 (Irs2)[8], forkhead transcription factor 1 (Foxo1)[6,9], and phosphoenolpyruvate carboxykinase (Pepck)[9] play important roles in the regulation of glucose metabolisms of the liver. It was shown that GABA improved hyperglycemia in STZ-induced diabetic rats and in the male
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