Coagulanolide modulates hepatic glucose metabolism in C57BL/KsJ-db/db mice

Abstract

Increased hepatic glucose output is one of the major causes of fasting hyperglycemia in diabetic patients. In this study, we investigated the mechanism of action of coagulanolide on hepatic glucose, regulating enzymes in type 2 diabetic C57BL/KsJ-db/db (db/db) mice. Coagulanolide is an active component of Withania coagulans fruit. Oral administration of coagulanolide for 3 weeks decreases fasting blood glucose and plasma insulin significantly, and it improves glucose tolerance in the db/db mice group. The enzyme activity and protein expression of glucokinase and pyruvate kinase was significantly enhanced in coagulanolide-treated db/db group when compared with untreated one. On the other hand, activities and protein expression of fructose-1,6-bisphosphatase, glucose 6-phosphatase, phosphoenolpyruvate carboxykinase, and glycogen phosphorylase enzymes were significantly lowered in treated group. The treatment with coagulanolide also normalizes the concentrations of plasma cholesterol, triglyceride, free fatty acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the db/db mice. These findings suggested that the coagulanolide is useful in the control of fasting hyperglycemia in type 2 diabetes by regulating the production of hepatic glucose.

New Insights for Oxidative Stress and Diabetes Mellitus

“…DM results in additional vascular events that result in cardiac disease [ 46 , 90 – 97 ], atherosclerosis [ 2 ], and renal disorders [ 61 , 98 – 101 ]. DM leads to immune system dysfunction [ 12 , 96 , 102 – 105 ], liver disorders [ 106 – 109 ], stroke [ 7 , 14 , 59 , 87 , 110 , 111 ], Alzheimer's disease [ 68 , 75 , 112 , 113 ], psychiatric disease [ 114 , 115 ], visual loss [ 86 , 116 – 118 ], and peripheral nerve impairment [ 88 ].…”

Hypoglycemic activity of withanolides and elicitated Withania somnifera

“…While studies have described anti-diabetic activity in withanolides including coagulanolide (Beg et al, 2014;Singh et al, 2012;Maurya et al, 2008), and 4b-hydroxywithanolide E (Takimoto et al, 2014), this is the first study documenting the anti-diabetic activity of withaferin A. Previously implicated as a possible treatment for cancer (Grover et al, 2010), inflammation (Maitra et al, 2009), and for inhibiting angiogenesis (Mohan et al, 2004), withaferin's hypoglycemic activity had not previously been documented.…”

Luteolin-Enriched Artichoke Leaf Extract Alleviates the Metabolic Syndrome in Mice with High-Fat Diet-Induced Obesity

“…Type 2 diabetes is characterized by an abnormal secretion of insulin that regulates glucose homeostasis [ 36 ]. Fasting hyperglycemia occurs as a result of the abnormal activities of hepatic glucose-regulating enzymes [ 37 ]. In this study, AR supplementation significantly decreased gluconeogenesis by suppressing hepatic PEPCK and G6Pase activities and increased hepatic IRS2 mRNA expression.…”