Protective role of Pollen Typhae total flavone against the palmitic acid-induced impairment of glucose-stimulated insulin secretion involving GPR40 signaling in INS-1 cells.

Prolonged elevated levels of free fatty acids (FFAs) contribute to the impairment of insulin secretion function of pancreatic ß cells, a hallmark of type 2 diabetes, which is partly attributed to the dysfunction of G-protein-coupled receptor 40 (GPR40) signaling. Pollen Typhae total flavone (PTF), an extract from a Chinese herbal medicine named Pollen Typhae, has been reported to effectively treat type 2 diabetes, but the underlying mechanisms remain to be fully elucidated. In the present study, palmitic acid (PA), a saturated fatty acid, severely impaired glucose-stimulated insulin secretion (GSIS) in a time-dependent manner in INS-1 cells, and PTF treatment prevented the impairment in a dose-dependent manner. Moreover, PTF improved insulin secretion function in rats presenting with type 2 diabetes induced by a high-fat diet and low-dose streptozotocin. Furthermore, PA exposure for 24 h decreased the protein expression of GPR40, phospholipase C (PLC)ß1, PLCß3, and protein kinase C (PKC), and inhibited the activity of PLC and PKC stimulated by GW9508, a GPR40 agonist. In addition, PTF enhanced the protein expression of GPR40 and to a certain extent strengthened the protein expression of PKC, increased cellular levels of triphosphoinositide (IP3) and diacylglycerol (DAG), and promoted GW9508-stimulated activity of PLC and PKC reduced by PA in INS-1 cells, which were blocked by PLC inhibitor U-73122 and PKC inhibitor staurosporine, respectively. Additionally, the improvement in PA-induced impairment of GSIS by PTF in INS-1 cells was restrained by U-73122, staurosporine, and calcium channel inhibitor nifedipine, respectively. The results indicate that PTF exerts a protective role against PA-induced impairment of GSIS involving GPR40 signaling in INS-1 cells.

GPR40: a therapeutic target for mediating insulin secretion (review).

G-protein-coupled receptor 40 (GPR40), known as free fatty acid receptor 1, is mainly expressed in pancreatic ß-cells and activated by medium- and long-chain fatty acids. Increasing evidence indicates that the activation of GPR40 in cells causes insulin secretion, and GPR40 has become an attractive therapeutic target for type 2 diabetes. Recently, certain novel GPR40 agonists have been identified that regulate glucose-stimulated insulin secretion, leading to the development of new drugs for the treatment of type 2 diabetes. In this review, we focus on progress in the physiological role of GPR40 and potential drugs targeting GPR40 over the past decade.

Yidiyin, a Chinese herbal decoction, improves erectile dysfunction in diabetic patients and rats through the NO-cGMP pathway.

The nitric-oxide (NO)-cyclic-guanosine-monophosphate (cGMP) pathway plays a key role in penile erection. Erectile dysfunction (ED) is a complication in male diabetic patients that impacts their quality of 1ife. Recently, Yidiyin, a Chinese herbal decoction, is used to treat diabetic ED, but convincing evidence is lacking, and the potential mechanisms remain uncertain. In the study, diabetic ED patients had low scores on international index of erectile function-5 (IIEF-5), and administration of Yidiyin and hypoglycemic drugs for 16 weeks ameliorated patients' scores on IIEF-5 more than the hypoglycemic drug alone. Moreover, streptozotocin-induced diabetes severely impaired rats' erectile function and the activity of the NO-cGMP pathway in the corpora cavernosum, and treatment with Yidiyin for 4 weeks obviously increased the rats' erectile function, remarkably enhanced the activity of nitric oxide synthase (NOS), and elevated the contents of NO and cGMP. Our findings indicate that Yidiyin improves diabetic ED probably by enhancing the NO-cGMP pathway.

[Effects of Jiangtang Bushen Recipe on serum C-reactive protein, tumor necrosis factor-alpha and interleukin-6 in patients with type 2 diabetes mellitus].

UNLABELLED: OBJECTIVE To observe the effect of Jiangtang Bushen Recipe (JBR) on inflammatory cytokines in patients with type 2 diabetes mellitus (T2DM), and explore its therapeutic mechanism. METHODS Sixty-four patients with T2DM were randomly divided into the treated group (n = 34) and the control group (n = 30). Education course, dietary treatment and conventional hypoglycemic agent were given to both groups, and JBR, mainly composed of Cibot Rhizome, Radix Dipsaci, Glossy Privet Fruit; Ecliptae Herba, Radicis Lycii, Radix Astragali, Rehmannia Dride Rhizome, etc., was given additionally to patients in the treated group, one dose a day for 4 weeks by boiled water and taking in two times. Fasting blood glucose (FBG), fasting insulin (FINS), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and C-reactive protein (CRP) were measured, and insulin sensitive index (ISI) and clinical TCM symptom score were calculated before and after treatment. RESULTS: After treatment, the clinical symptom score dropped in both groups (P < 0.01), and it was lower in the treated group than that in the control group (P < 0.01). At the same time, serum levels of FINS, CRP, TNF-alpha and IL-6 decreased and ISI increased significantly, the effect showed in the treated group was also superior to that in the control group (P < 0.05). CONCLUSION: JBR, which could tonify Pi and Shen, nourish Yin and clear away heat, can improve insulin resistance and alleviate clinical symptoms of T2DM patients, the mechanism may be related with its actions in regulating the production of inflammatory cytokines and inhibiting inflammatory reac-