3.5 Effect of PA extract on biochemical parameters
Plasma insulin is one of the essential factors for estimation sugar associated with diabetes. Several researchers suggested that the plasma insulin level reduces during the expansion of diabetes due to break down of pancreatic β-cells. The plasma insulin level was almost same in normal and PA (200 mg/kg) group rats. STZ induced DM rats showed the reduction in plasma insulin that may be attributed to dysfunction of pancreatic β-cells. DM rats treated with PA showed the significantly (p<0.001) enhancement of plasma insulin level in dose-dependent manner. STZ group rats demonstrated the plasma insulin 3.1±0.32 (μU/mL), which was less than 4 times as compared to normal andPA (200 mg/kg) group rats. PA treatment showed the insulin level as 5.05±0.93, 8.13±0.56 and 12.54±0.85 (μU/mL), respectively (Supplementary table 5). The results suggest that PA improved the plasma insulin and decrease the BGL and confirms its anti-diabetic effect.
A similar style was observed in case of hexokinase content. The hexokinase level was decreased in the STZ induced DM group rats and does depend on the treatment of PA significantly (p<0.001) (Supplementary table 5).
The level of glycated Haemoglobin, fructose-1-6-biphosphatase, and glucose-6-Phosphatase was increased in the STZ induced DM group rats, which was significantly (p<0.001) down-regulated by thePA in t a dose-dependent manner (Supplementary table 5).
Supplementary table 6 illustrates the effect of the PA on the HOMA IR and HOMA β. HOMA IR level of DC control group rats increased and the level of HOMA β reduced in the DC group rats, the dose-dependent treatment of PA altered the level of HOMA IR and HOMA β a resemblance with glibenclamide treated group.
The liver tissue plays a crucial role in the circulation of glucose in various pathological and physiological states especially in case of diabetes. Several drugs, compounds, and many more products are detoxified and metabolized in the liver by a different mechanism (Ahmed et al., 2013, 2014b; Kumar et al., 2014). Existing literature suggests that diabetes directly linked to the variety of hepatic abnormalities such as fibrosis, glycogen deposition, increased non-alcoholic fatty liver disease (NAFLD), liver enzymes, Hepatocellular carcinomas, cirrhosis, viral hepatitis, acute liver disease and fibrosis to name few. One important role by the liver is well associated with control of postprandial hyperglycemia and glycogen synthesis. The liver enzymes such as fructose-1-6-biphosphatase, Hexokinase and glucose-6-phosphate play a vital role during the conversion of glucose to required energy, glycogen synthesis and glucose utilization (Tappy and Lê, 2012). Several research suggests that the reduced level of hexokinase increase the glucose level into the circulating blood via inhibiting the conversion of glucose into glucose-6-phosphate (Newsholme et al., 1968). Our results of STZ induced DM group rats and PA -treated group rats showed the increased level of hexokinase, responsible for its anti-diabetic effects. glucose-6-phosphate is regulated during glucose metabolism with the help of hexokinase. Increase level of glucose-6-phosphate, can be related to its increase gluconeogenetic enzyme activity and boost the production of fats and in renal and hepatic tissue (Ahmed et al., 2013, 2014c, 2015; Kumar et al., 2013, 2014). Fructose-1,6 biphosphatase and glucose-6-phosphatase, both play a key role in the gluconeogenic pathway, in diabetes, there is increased synthesis of both these enzymes, responsible for increasing the glucose production by the tissue. STZ induced DM rats showed the increased activity of both enzymes and dose-dependent treatment of PAshowed the reduction of the activity in fructose-1,6 biphosphatase and glucose-6-phosphatase. These results confirm and suggest the anti-diabetic effect of PA . The possible mechanism may be due to the reduction of the glyconeogenesis and increase glycolysis.