Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway.

Phytomodulatory proteins from the latex of the medicinal plant Calotropis procera has been shown to be implicated in many pharmacological properties. However there is no current information about their activity on glucose metabolism, although the latex is used in folk medicine for treating diabetes. In this study the phytomodulatory proteins (LP) from C. procera latex were assessed on glycemic homeostasis. Control animals received a single intravenous dose (5 mg/kg) of LP or saline solution (CTL). Four hours after treatment, the animals were euthanized and their livers were excised for analysis by western blot and RT-PCR AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK) and tumor necrosis factor alpha (TNF-α). In vivo tests of intraperitoneal tolerance to insulin, glucose and pyruvate were also performed, and the effect of LP administration on fed glycemia was studied followed by blood analysis to determine serum insulin levels. Treatment with LP reduced glycemia two hours after glucose administration (LP: 87.2 ± 3.70 mg/dL versus CTL: 115.6 ± 8.73 mg/dL). However, there was no change in insulin secretion (CTL: 14.16 ± 0.68 mUI/mL and LP: 14.96 ± 0.55 mUI/mL). LP improved the insulin sensitivity, represented by a superior glucose decay constant during an insulin tolerance test (kITT) (4.17 ± 0.94%/min) compared to the CTL group (0.82 ± 0.72%/min), and also improved glucose tolerance at 30 min (105.2 ± 12.4 mg/dL versus 154.2 ± 18.51 mg/dL), while it decreased hepatic glucose production at 15 and 30 min (LP: 75.5 ± 9.31 and 52.5 ± 12.05 mg/dL compared to the CTL: 79.0 ± 3.02 and 84.5 ± 7.49 mg/dL). Furthermore, there was a significant inhibition of gene expression of PEPCK (LP: 0.66 ± 0.06 UA and CTL: 1.14 ± 0.22 UA) and an increase of phosphorylated AMPK (LP: 1.342 ± 0.21 UA versus CTL: 0.402 ± 0.09 UA). These findings confirm the effect of LP on glycemic control and suggest LP may be useful in diabetes treatment. However, the pharmacological mechanism of LP in PEPCK modulation still needs more clarification.

Sex differences in subcutaneous adipose tissue redox homeostasis and inflammation markers in control and high-fat diet fed rats.

The development of obesity-related metabolic disorders is more evident in male in comparison with female subjects, but the mechanisms are unknown. Several studies have shown that oxidative stress is involved in the pathophysiology of obesity, but the majority of these studies were performed with male animals. The aim of this study was to evaluate the sex-related differences in subcutaneous adipose tissue redox homeostasis and inflammation of rats chronically fed a high-fat diet. NADPH oxidase (NOX), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase activities were evaluated in the subcutaneous adipose tissue (SC) of adult male and female rats fed either a standard chow (SCD) or a high-fat diet (HFD) for 11 weeks. NOX2 and NOX4 messenger RNA (mRNA) levels, total reduced thiols, interleukin (IL)-1ß, tumor necrosis factor α (TNF-α), and IL-6 were also determined. Higher antioxidant enzyme activities and total reduced thiol levels were detected in SC of control male compared with female rats. Chronic HFD administration increased NOX activity and NOX2 and NOX4 mRNA levels and decreased SOD and GPx activities only in male animals. IL-1ß, TNF-α, and IL-6 levels, as well as Adgre1, CD11b, and CD68 mRNA levels, were also higher in SC of males after HFD feeding. In SC of females, catalase activity was higher after HFD feeding. Taken together, our results show that redox homeostasis and inflammation of SC is sexually dimorphic. Furthermore, males show higher oxidative stress in SC after 11 weeks of HFD feeding owing to both increased reactive oxygen species (ROS) production through NOX2 and NOX4 and decreased ROS detoxification.