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Anti-diabetic actions of Camellia sinensis leaves, used traditionally for type 2 diabetes (T2DM) treatment, have been determined. Insulin release, membrane potential and intra-cellular Ca were studied using the pancreatic β-cell line, BRIN-BD11 and primary mouse pancreatic islets. Cellular glucose-uptake/insulin action by 3T3-L1 adipocytes, starch digestion, glucose diffusion, dipeptidyl peptidase-4 (DPP-IV) activity and glycation were determined together with in vivo studies assessing glucose homoeostasis in high-fat-fed (HFF) rats. Active phytoconstituents with insulinotropic activity were isolated using reversed-phase HPLC, LCMS and NMR. A hot water extract of C. sinensis increased insulin secretion in a concentration-dependent manner. Insulinotropic effects were significantly reduced by diazoxide, verapamil and under Ca-free conditions, being associated with membrane depolarisation and increased intra-cellular Ca2+. Insulin-releasing effects were observed in the presence of KCl, tolbutamide and isobutylmethylxanthine, indicating actions beyond K+ and Ca2+ channels. The extract also increased glucose uptake/insulin action in 3T3L1 adipocyte cells and inhibited protein glycation, DPP-IV enzyme activity, starch digestion and glucose diffusion. Oral administration of the extract enhanced glucose tolerance and insulin release in HFF rats. Extended treatment (250 mg/5 ml per kg orally) for 9 d led to improvements of body weight, energy intake, plasma and pancreatic insulin, and corrections of both islet size and β-cell mass. These effects were accompanied by lower glycaemia and significant reduction of plasma DPP-IV activity. Compounds isolated by HPLC/LCMS, isoquercitrin and rutin (464·2 Da and 610·3 Da), stimulated insulin release and improved glucose tolerance. These data indicate that C. sinensis leaves warrant further evaluation as an effective adjunctive therapy for T2DM and source of bioactive compounds.

Spirulina platensis has been found to be useful in the treatment of type 2 diabetes. The present study aims to elucidate the effects of ethanol extract and butanol fraction of S. platensis on insulin release and glucose homoeostasis in type 2 diabetic rats, together with their mechanism of actions. In vitro and in vivo methods were used including cellular studies to determine potential role of ion channels and cAMP in the insulinotropic actions of the extracts. The ethanol extract and butanol fraction stimulated insulin release from mouse islets and pancreatic β-cells in a concentration-dependent manner. The butanol fraction also similarly stimulated insulin release from perfused rat pancreas. The insulin-releasing action was augmented by glucose, isobutylmethylxanthine, tolbutamide and a depolarising concentration of KCl. The insulin secretory effect was attenuated with diazoxide and verapamil and by omission of extracellular Ca2+. Butanol fraction was found to significantly inhibit dipeptidyl peptidase IV enzyme activity. Moreover, butanol fraction improved glucose tolerance following oral glucose administration (2·5 g/kg body weight (b.w.)). The butanol fraction was tested on 24 h starved rats given an oral sucrose load (2·5 g/kg b.w.) to examine possible effects on carbohydrate digestion and absorption. S. platensis substantially decreased postprandial hyperglycaemia after oral sucrose load and increased unabsorbed sucrose content throughout the gut. During in situ intestinal perfusion with glucose, the butanol fraction reduced glucose absorption and promoted gut motility. Finally, chronic oral administration of butanol fraction for 28 d significantly decreased blood glucose, increased plasma insulin, pancreatic insulin stores, liver glycogen and improved lipid profile. The characterisation of active compounds from butanol fraction revealed the presence of p-coumaric acid, β-carotene, catechin and other antioxidant polyphenols. In conclusion, S. platensis could be an adjunctive therapy for the management of type 2 diabetes.

The effects of active immunisation with gastric inhibitory polypeptide (GIP) or (proline3)GIP–ovalbumin conjugates on insulin resistance, metabolic dysfunction, energy expenditure and cognition were examined in high-fat-fed mice. Normal mice were injected (subcutaneously) once every 14 d for 98 d with GIP–ovalbumin conjugates, with transfer to a high-fat diet on day 21. Active immunisation resulted in GIP antibody generation and significantly (P P P P P 3)GIP immunised mice and were independent of any effects on food intake or body weight. Further tests established that coupling of GIP peptides to ovalbumin abolished any intrinsic insulin-releasing or glucose-lowering activity. These results suggest that induction of GIP-neutralising antibodies with GIP–ovalbumin conjugates is an effective means of countering the metabolic abnormalities induced by high-fat feeding and does not adversely have an impact on a marker of cognition function or energy expenditure.

In the following sections, the mechanisms underlying the acute actions of nutrie,ts and entero-insular stimuli on insulin secretion will be considered together with the ways in which the β cells integrate the various signals to provide the appropriate secretory response

The aim of the experiment was to test the theory that accustoming pigs to a high-fat diet causes exaggerated gastric inhibitory polypeptide (GIP) secretion in response to a high-fat meal, and to determine whether hypersecretion of GIP could be related to an increase in the GIP content of the small intestine. Twenty-four pigs were fed one of three dietary regimens for 11 weeks: a high-carbohydrate diet (CL), or a high-fat diet (FL), both fed at 1.46 MJ gross energy (GE)/kg live weight0.75per d, or a high-fat diet (FH) fed at 2.10 MJ GE/kg live weight0.75per d. At the end of the period two acute tests were performed. For acute test 1 the accustomed meal (diets CLFLand FH) and for acute test 2 a standard high-fat meal (diet FL) were given; blood samples were taken during the next 5 h and analysed for GIP, insulin and glucose. Integrated increases in hormone and glucose levels were compared by analysis of variance (0–300 min). In acute test 1 there were significantly different plasma GIP concentrations between groups (CL> FH> FL;P< 0.05). Plasma insulin concentrations were significantly higher in group CLcompared with groups FLand FH(P< 0.002). There were no differences in glucose levels. In acute test 2 integrated increases in plasma GIP (0–300 min) concentrations were not significantly different; however, GIP (0–45 min) concentrations were significantly higher in group FHthan in groups CLand FL(P< 0.05). There were no differences in plasma insulin concentrations. Plasma glucose (0–300 min) concentrations were significantly higher in groups FLand FHcompared with group CL(P< 0.05). The GIP content of tissue samples taken at the end of the experiment from the duodenum, jejunum, upper and lower ileum decreased significantly in a proximal to distal direction (P< 0.001). Diet FHsignificantly increased the average GIP content of the small intestine compared with diets CLand FL(P< 0.05). It is concluded that fat meal-stimulated GIP secretion was enhanced by increased feeding level during a pre-treatment phase, possibly due to an increase in GIP synthesis in the small intestine. The high-fat diet caused glucose intolerance after a high-fat meal. This may be due in part to the action of dietary fat on glucose transport and metabolism.

Plantago ovata has been reported to reduce postprandial glucose concentrations in diabetic patients. In the present study, the efficacy and possible modes of action of hot-water extracts of husk of P. ovata were evaluated. The administration of P. ovata (0.5 g/kg body weight) significantly improved glucose tolerance in normal, type 1 and type 2 diabetic rat models. When the extract was administered orally with sucrose solution, it suppressed postprandial blood glucose and retarded small intestinal absorption without inducing the influx of sucrose into the large intestine. The extract significantly reduced glucose absorption in the gut during in situ perfusion of small intestine in non-diabetic rats. In 28 d chronic feeding studies in type 2 diabetic rat models, the extract reduced serum atherogenic lipids and NEFA but had no effect on plasma insulin and total antioxidant status. No effect of the extract was evident on intestinal disaccharidase activity. Furthermore, the extract did not stimulate insulin secretion in perfused rat pancreas, isolated rat islets or clonal beta cells. Neither did the extract affect glucose transport in 3T3 adipocytes. In conclusion, aqueous extracts of P. ovata reduce hyperglycaemia in diabetes via inhibition of intestinal glucose absorption and enhancement of motility. These attributes indicate that P. ovata may be a useful source of active components to provide new opportunities for diabetes therapy.

1. To investigate the role of dietary components in the hyperinsulinaemia of the obese hyperglycaemic (ob/ob) syndrome, plasma insulin responses to fasting and refeeding were examined in Aston ob/ob mice supplied with standard diet, non-digestible-carbohydrate test food, and isoenergetic test foods from which either carbohydrate, protein or fat was omitted.2. During fasting, plasma insulin concentrations fell more rapidly and to a greater extent than plasma glucose. Refeeding the standard diet raised insulin concentrations above normal, associated with a 25% compensatory increase in food intake over 24 h.3. Test foods supplied to previously fed or fasted mice produced glucose responses consistent with the available carbohydrate content. Carbohydrate-free food (protein and fat) provided a small insulinotropic stimulus; the effect of protein-free food (carbohydrate and fat) was greater; and the combination of carbohydrate with protein (fat-free food) evoked a marked insulin response. In contrast, insulin concentrations declined in mice given the non-digestible-carbohydrate food.4. Consumption of the standard diet was increased after 24 h feeding non-digestible-carbohydrate food, but was unaffected by a 30 h fast initiated 54 h previously.5. These results demonstrate that hyperinsulinaemia in ob/ob mice is not merely triggered by the ingestion of bulk, but depends on the type of nutrient ingested. Dietary carbohydrate appears to be the major stimulus to the hyperinsulinaemia, with an important augmentation in the presence of protein. Since direct glucose stimulation of insulin release is defective in ob/ob mice, the hyperinsulinaemia must be mediated by increased activity of the enteroinsular axis.