Traditionally, the mechanisms underlying the dynamics of plasma glucose excursions after oral ingestion of glucose have been - roughly speaking - divided into three parts: 1) absorption of glucose from the small intestinal lumen to the blood stream resulting in elevation of plasma glucose concentration, 2) pancreatic beta cell sensing of elevated plasma glucose and, consequently, release of just adequate amounts of insulin from the beta cell into the blood stream to 3) facilitate insulin-induced uptake of glucose by liver, adipose and muscle tissues resulting in reversion of plasma glucose concentrations to baseline levels. However, a simple physiological experiment tells us that something important in the above-outlined three-step conception of physiological glucose disposal is missing: When healthy subjects on separate occasions ingest increasing amounts of glucose the resultant plasma glucose excursions are amazingly similar but still the insulin response increases with the glucose load. Thus, other factors than plasma glucose must also determine insulin secretion. This is one of the major actions of the incretins.
Figure 1. Plasma glucose responses to three different oral glucose loads.As said, when healthy subjects on separate occasions ingest very different amounts of glucose (e.g. as used by Nauck et al. 25, 50 and 100 g of glucose, respectively) the resultant plasma glucose excursions are amazingly similar, as illustrated in Figure 1. The reason for this becomes apparent when beta cell secretory responses are scrutinized: these reveal progressively increased insulin responses during the escalating oral glucose loads 1,2 as illustrated by the plasma C-peptide responses in Figure 2.
Figure 2. C-peptide responses to three different oral glucose loadsHowever, at the same time it becomes obvious that plasma glucose levels do not constitute a major regulator of insulin secretion from beta cells (since three similar plasma glucose excursions give rise to three very different insulin secretory patterns). Something else seems to play a major role in conveying the amount of ingested glucose to the beta cells for them to secrete the right amount of insulin for disposing effectively of the absorbed glucose. Thus, in this ‘chapter’ of Diapedia a pivotal part of the traditional (mis)conception of postprandial glucose disposal from the blood stream, namely the mechanisms behind postabsorptive insulin secretion, will be elaborated and redefined by reviewing the physiology of the gut incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
^ Bagger JI, Knop FK, Lund A, Vestergaard H, Holst JJ, Vilsboll T (2011) Impaired regulation of the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab 96:737-745
^ Nauck MA, Homberger E, Siegel EG, et al (1986) Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 63:492-498