72 This is not surprising—as emptying of nutrients from the stomach occurs at an overall rate of ∼1–4 kcal/min in health (and frequently slower than this in diabetes), only a few hours each day, prior to breakfast, are truly reflective of the “fasting” glycemic state. Thus, the management of postprandial blood glucose excursions has in

recent years PKC412 attracted increasing interest.72,73 Postprandial glycemia is potentially influenced by several factors, including preprandial glycemia, the carbohydrate content of a meal, the rate of small intestinal delivery and absorption of nutrients, insulin and glucagon secretion and peripheral insulin sensitivity. While the relative contribution of these factors is variable, it is now appreciated that gastric emptying accounts for at least a third of the variance in peak postprandial levels after oral glucose in both healthy subjects74 and patients with type 12 and type 2 diabetes.57 In type 1 patients with gastroparesis, less insulin is initially required to maintain euglycemia postprandially when compared to those with normal gastric emptying.75 Gastric emptying also accounts for a substantial amount of variation in glycemic response to carbohydrate of variable glycemic indices.48 What has only recently been appreciated is that the relationship of glycemia with small intestinal glucose delivery

MLN0128 mw is non-linear, as evidenced by the glycemic response to intraduodenal infusion of glucose at rates within the normal range for gastric emptying in both healthy76 and type 2 diabetic subjects.77 At an intraduodenal glucose infusion rate of 1kcal/min, there is only a modest elevation in blood glucose,

but a substantial elevation in blood glucose occurs in response to an infusion selleck inhibitor rate of 2 kcal/min. However there is minimal further increase when the rate is increased to 4 kcal/min (Fig. 1).76 These discrepant blood glucose responses are likely to reflect the substantially increased plasma insulin response to the 4 kcal/min infusion, which is probably accounted for by incretin hormone secretion.76 At 1 kcal/min, there is minimal, transient, stimulation of GLP-1 compared with sustained elevation of GIP. In contrast at 4 kcal/min, there is a substantial increase in GLP-1 secretion with further increase in GIP.64,76 Thus, the marked increase in insulin secretion at higher rates of intraduodenal glucose infusion is likely to be attributable to GLP-1,64 secretion of which increases in a non-linear fashion whilst GIP rises linearly.78 In both healthy and type 2 diabetic subjects, an initially more rapid delivery of glucose to the small intestine results in higher GIP, GLP-1 and insulin responses in comparison to constant delivery of an identical glucose load (Fig. 2).