Background[6]-Gingerol, a major component of Zingiber officinale, was previously reported to ameliorate hyperglycemia in type 2 diabetic mice. Endocrine signaling is involved in insulin secretion and is perturbed in db/db Type-2 diabetic mice. [6]-Gingerol was reported to restore the disrupted endocrine signaling in rodents. In this current study on Leprdb/db diabetic mice, we investigated the involvement of endocrine pathway in the insulin secretagogue activity of [6]-Gingerol and the mechanism(s) through which [6]-Gingerol ameliorates hyperglycemia.MethodsLeprdb/db type 2 diabetic mice were orally administered a daily dose of [6]-Gingerol (200 mg/kg) for 28 days. We measured the plasma levels of different endocrine hormones in fasting and fed conditions. GLP-1 levels were modulated using pharmacological approaches, and cAMP/PKA pathway for insulin secretion was assessed by qRT-PCR and ELISA in isolated pancreatic islets. Total skeletal muscle and its membrane fractions were used to measure glycogen synthase 1 level and Glut4 expression and protein levels.Results4-weeks treatment of [6]-Gingerol dramatically increased glucose-stimulated insulin secretion and improved glucose tolerance. Plasma GLP-1 was found to be significantly elevated in the treated mice. Pharmacological intervention of GLP-1 levels regulated the effect of [6]-Gingerol on insulin secretion. Mechanistically, [6]-Gingerol treatment upregulated and activated cAMP, PKA, and CREB in the pancreatic islets, which are critical components of GLP-1-mediated insulin secretion pathway. [6]-Gingerol upregulated both Rab27a GTPase and its effector protein Slp4-a expression in isolated islets, which regulates the exocytosis of insulin-containing dense-core granules. [6]-Gingerol treatment improved skeletal glycogen storage by increased glycogen synthase 1 activity. Additionally, GLUT4 transporters were highly abundant in the membrane of the skeletal myocytes, which could be explained by the increased expression of Rab8 and Rab10 GTPases that are responsible for GLUT4 vesicle fusion to the membrane.ConclusionsCollectively, our study reports that GLP-1 mediates the insulinotropic activity of [6]-Gingerol, and [6]-Gingerol treatment facilitates glucose disposal in skeletal muscles through increased activity of glycogen synthase 1 and enhanced cell surface presentation of GLUT4 transporters.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1903-0) contains supplementary material, which is available to authorized users.

BackgroundCentella asiatica (C. asiatica) was previously reported to have anti-hyperglycemic effects in animal diabetic model rats. However, its activity on organ and tissue level remains unstudied. Our study aims at exploring the possible effects, C. asiatica extract and insoluble fiber has on carbohydrate absorption, insulin secretion, insulin sensitivity and glucose utilization.MethodsFor primary evaluation of anti-hyperglycemic activity, we measured Fasting Blood Glucose and performed Glucose Tolerance Test, in type 2 diabetic rats. To further study the pancreatic effect and glucose utilization, plasma insulin concentration, insulin secreted from isolated rat islets and liver glycogen were assayed. Effect on carbohydrate break down was assayed using intestinal disaccharidase enzyme, α-amylase inhibition assays and Six-Segment study of the GI tract. Effect of C. asiatica on glucose absorption was studied by an in-situ, perfused, intestinal model in rats and by glucose-fiber binding assay. Gastrointestinal motility was seen by a BaSO4 milk traverse test. Additionally, a complete lipid profile assay, after a chronic study, was conducted.ResultsC. asiatica showed no significant change in insulin secretion in-vivo and in isolated rat islets. Additionally, no effect of the extract was seen on liver glycogen deposition. Retarded glucose absorption was seen in the in-situ perfused rat intestinal model at a dose. The extract was also found to inhibit action of both intestinal disaccharidase and α-amylase. This was confirmed, yet again, via the Six Segment study, where sucrose digestion was found to be inhibited throughout the length of the GI Tract. Significant glucose-fiber binding was demonstrated in the in-vitro models. During the chronic study, body mass of C. asiatica treated Type 2 diabetic rats returned to normal and their polydipsic and polyphagic conditions were also improved. Chronic treatment of C. asiatica also improved subject’s lipid profile.ConclusionA combination of in-vitro, in-vivo and in-situ tests confirmed the anti-hyperglycemic activity of C. asiatica and its tissue level mechanism. Further study is required to fully elucidate the effect this extract or the active compounds have on the individual glucose transporters and the precise mechanism of glucose-fiber binding.

BackgroundThe study was designed to investigate the probable mechanisms of anti-hyperglycemic activity of B. Vulgaris.Methodology/Principal FindingsAqueous fraction of B. Vulgaris extract was the only active fraction (50mg/kg). Plasma insulin level was found to be the highest at 30 mins after B. Vulgaris administration at a dose of 200mg/kg. B. Vulgaris treated mice were also assayed for plasma Acetylcholine, Glucagon Like Peptide-1 (GLP-1), Gastric Inhibitory Peptide (GIP), Vasoactive Intestinal Peptide, Pituitary Adenylate Cyclase-Activating Peptide (PACAP), Insulin Like Growth Factor-1 (IGF-1), Pancreatic Polypeptides (PP), and Somatostatin, along with the corresponding insulin levels. Plasma Acetylcholine and GLP-1 significantly increased in B. Vulgaris treated animals and were further studied. Pharmacological enhancers, inhibitors, and antagonists of Acetylcholine and GLP-1 were also administered to the test animals, and corresponding insulin levels were measured. These studies confirmed the role of acetylcholine and GLP-1 in enhanced insulin secretion (p<0.05). Principal signaling molecules were quantified in isolated mice islets for the respective pathways to elucidate their activities. Elevated concentrations of Acetylcholine and GLP-1 in B. Vulgaris treated mice were found to be sufficient to activate the respective pathways for insulin secretion (p<0.05). The amount of membrane bound GLUT1 and GLUT4 transporters were quantified and the subsequent glucose uptake and glycogen synthesis were assayed. We showed that levels of membrane bound GLUT4 transporters, glucose-6-phosphate in skeletal myocytes, activity of glycogen synthase, and level of glycogen deposited in the skeletal muscles all increased (p<0.05).ConclusionFindings of the present study clearly prove the role of Acetylcholine and GLP-1 in the Insulin secreting activity of B. Vulgaris. Increased glucose uptake in the skeletal muscles and subsequent glycogen synthesis may also play a part in the anti-hyperglycemic activity of B. Vulgaris.

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It is the challenge of Johannesburg to move beyond KO, yet it is the danger of Johannesburg to regress behind KO. The Rio Conference on Environment and Development strove to address two major crises: the crisis of nature and that of justice. Environmentalistsoften from the Northwere expected to take into account the desire of the majority of the world's citizens for a life beyond poverty and distress. By contrast, developmentalists -* often from the South-were called upon to recognize the disastrous repercussions * ofa deteriorated nature base. Typically, environmentalists were seen to be opposing deforestation, chemical agriculture or expansion of power plants, while : developmentalists were pushing for marketing timber, expanding food supplies or electrifying villages. Therefore, the Earth Summit aimed at integrating the environ-* ment and development agendas to liberate policy makers from the dilemma of either aggravating the crisis of nature by pushing for development or aggravating the crisis of justice by insisting on the protection of nature.As it turned out, the Rio process fell short of fulfilling this ambition. How to respond to the desire for justice without upsetting the biosphere is still a puzzle for the 21st century. Of course, the fact that helping people and helping nature can go hand in hand has been demonstrated in many instances: in organic agriculture, in sustainable forestry and in resourceefficient industries as well. But on a macro-scale, the reconcilia-