Oral supplementation with ginseng polysaccharide promotes food intake in mice.

INTRODUCTION: Ginseng polysaccharide (GPS, same as Panax polysaccharide) is a kind of polysaccharide extracted from ginseng. It has been reported that GPS has the ability to activate innate immunity, regulates blood sugar balance, and improves antioxidant capacity, but the effect on feeding behavior and its mechanism remains unclear. METHOD: To investigate the possible effect of GPS on feeding behavior of animals, mice were supplied with GPS in water, and food intake, hedonic feeding behavior, anxiety-like behavior, expression of appetite-regulation peptides in the central nervous system and glucose-related hormone levels in the serum of mice were measured. RESULTS: Ginseng polysaccharide significantly increased the average daily food intake in mice and promoted hedonic eating behavior. Meanwhile, the levels of serum glucose and glucagon were significantly reduced by GPS, and GPS promoted hypothalamic neuropeptide Y expression, inhibited proopiomelanocortin (POMC) expression, and reduced dopamine D1 receptor (DRD1) levels in the midbrain. We also found that the anxiety level of mice was significantly lower after GPS intake. In conclusion, oral supplementation with GPS promoted food intake in mice, most likely through the regulation of circulating glucose levels.

Thirty days of resveratrol supplementation does not affect postprandial incretin hormone responses, but suppresses postprandial glucagon in obese subjects.

AIMS: Resveratrol, a natural polyphenolic compound produced by various plants (e.g. red grapes) and found in red wine, has glucose-lowering effects in humans and rodent models of obesity and/or diabetes. The mechanisms behind these effects have been suggested to include resveratrol-induced secretion of the gut incretin hormone glucagon-like peptide-1. We investigated postprandial incretin hormone and glucagon responses in obese human subjects before and after 30 days of resveratrol supplementation. METHODS: Postprandial plasma responses of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide and glucagon were evaluated in 10 obese men [subjects characteristics (mean ± standard error of the mean): age 52 ± 2 years; BMI 32 ± 1 kg/m(2), fasting plasma glucose 5.5 ± 0.1 mmol/l] who had been given a dietary supplement of resveratrol (Resvida(®) 150 mg/day) or placebo for 30 days in a randomized, double-blind, crossover design with a 4-week washout period. At the end of each intervention period a standardized meal test (without co-administration of resveratrol) was performed. RESULTS: Resveratrol supplementation had no impact on fasting plasma concentrations or postprandial plasma responses (area under curve values) of glucose-dependent insulinotropic polypeptide (11.2 ± 2.1 vs. 11.8 ± 2.2 pmol/l, P = 0.87; 17.0 ± 2.2 vs. 14.8 ± 1.6 min × nmol/l, P = 0.20) or glucagon-like peptide-1 (15.4 ± 1.0 vs. 15.2 ± 0.9 pmol/l, P = 0.84; 5.6 ± 0.4 vs. 5.7 ± 0.3 min × nmol/l, P = 0.73). Resveratrol supplementation significantly suppressed postprandial glucagon responses (4.4 ± 0.4 vs. 3.9 ± 0.4 min × nmol/l, P = 0.01) without affecting fasting glucagon levels (15.2 ± 2.2 vs. 14.5 ± 1.5 pmol/l, P = 0.56). CONCLUSIONS: Our data suggest that 30 days of resveratrol supplementation does not affect fasting or postprandial incretin hormone plasma levels in obese humans, but suppresses postprandial glucagon responses.

GLP-1R and amylin agonism in metabolic disease: complementary mechanisms and future opportunities.

The discoveries of the incretin hormone glucagon-like peptide-1 (GLP-1) and the ß-cell hormone amylin have translated into hormone-based therapies for diabetes. Both classes of molecules also exhibit weight-lowering effects and have been investigated for their anti-obesity potential. In the present review, we explore the mechanisms underlying the physiological and pharmacological actions of GLP-1 and amylin agonism. Despite their similarities (e.g. both molecular classes slow gastric emptying, decrease glucagon and inhibit food intake), there are important distinctions between the central and/or peripheral pathways that mediate their effects on glycaemia and energy balance. We suggest that understanding the similarities and differences between these molecules holds important implications for the development of novel, combination-based therapies, which are increasingly the norm for diabetes/metabolic disease. Finally, the future of GLP-1- and amylin agonist-based therapeutics is discussed.

(2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

A novel series of beta-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC(50) = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.

Glucagon-like peptide-1 response to acarbose in elderly type 2 diabetic subjects.

The anti-hyperglycemic effect of alpha-glucosidase inhibitors (AGI) is partly attributed to their ability to stimulate the secretion of glucagon-like peptide-1 (GLP-1), a gut hormone with insulin stimulating capability. To determine if this mechanism of action contributes significantly to the therapeutic efficacy of AGI in the elderly, 10 type 2 diabetic subjects over the age of 65 years were given a standardized test meal with or without 25, 50, or 100 mg acarbose. The serum glucose, insulin, triglycerides and GLP-1 levels were measured at baseline and at 1 and 2 h postprandially. The anti-hyperglycemic effect of acarbose was maximal at 25-mg dose under these experimental conditions. Serum postprandial insulin and triglycerides levels were not significantly altered with acarbose treatment. The postprandial serum GLP-1 levels rose significantly only in two subjects and only during treatment with 100-mg acarbose. There were no significant correlations between serum GLP-1 and serum glucose or insulin levels. It is concluded that in most elderly type 2 diabetic subjects, maximal anti-hyperglycemic effects can be achieved with relatively small doses of acarbose and that GLP-1 is unlikely to contribute to the clinical efficacy of this agent in this subgroup of subjects.

GLP-1 release in man after lower large bowel resection or intrarectal glucose administration.

BACKGROUND: This study addresses the question whether the insulinotropic gut hormone, glucagon-like peptide-1 (GLP-1), is released from the lower large bowel upon oral or rectal glucose uptake. METHODS: It was evaluated whether rectum or sigmoid colon resection alters glucose homeostasis or the plasma levels of the insulinotropic gut hormone, gastric inhibitory polypeptide (GIP), or GLP-1. Six men and 3 women (age 63 +/- 8 years, BMI 25.4 +/- 4.0 kg/m2) with normal preoperative fasting glucose values were treated before and after resection of large bowel segments. Fasting oral glucose tolerance (OGT, 75 g glucose/300 ml) tests were performed both before and 10 days postoperatively. Another approach aimed to clarify whether luminal glucose stimulation in the rectum/sigmoid colon increases GLP-1 plasma levels. Ten healthy volunteers (4 males, 6 females, age 25 +/- 2 years, BMI 22.1 +/- 2.4 kg/m2) received enemas with both saline and, 7 days later, 1 g/kg body weight glucose (70% glucose solution) intrarectally. RESULTS: Neither rectum nor sigmoid colon resection led to significant changes in the pre- and postoperative glucose responses to OGT testing, or insulin, GIP and GLP-1 release. Intrarectal glucose instillation increased blood glucose by about 10 mg/dl with parallel small elevations in immunoreactive insulin and immunoreactive C peptide. However, plasma GLP-1 levels remained unaltered. CONCLUSION: Our data make it unlikely that GLP-1 derived from the lower large bowel contributes significantly to maintain normal glucose tolerance.

[Colchicine: rationale for its use in liver disease]. / Colchicina. Fundamentos para su uso en enfermedades hepáticas.

Colchicine is a substance derived from the Colchicum Autumnale plant, its pharmacological uses have been demonstrated over the years. Initially used for the treatment of acute gout, it has been utilized for a wide variety of diseases, including mediterranean familial fever, alcoholic, posthepatitic and primary biliary liver cirrhosis. We have demonstrated in different studies that colchicine reduces markedly mortality rates in cirrhotics and the levels of interleukin-1 in patients with primary biliary cirrhosis.