Normal Insulin Secretion in Humans

Abstract

Normal insulin secretion in humans is mainly regulated by glucose, but additional factors including other nutrients, hormones, and neural input play an important role. In the basal state, insulin is released in a rapid pulsatile manner, with pulses occurring every 6–10 min. These pulses are superimposed on an oscillatory pattern of 11–15 oscillations per 24 h. Dynamic insulin release also occurs in response to stimuli. The insulin response to intravenous glucose has been shown to have two distinct phases: an early first phase response lasting for 10 min, and a slower longer second phase response lasting as long as the glucose level is elevated. Preexistent elevations in the plasma glucose level are able to increase the insulin response to a subsequent glucose stimulus, an effect called priming. Glucose is also capable of potentiating the insulin response to non‐glucose secretagogues such as amino acids, peptides, and sulfonylureas. Non‐glucose factors that affect insulin secretion include amino acids, free fatty acids, medications, and the response to stress. Neural inputs regulate islet secretory function through both the sympathetic and parasympathetic nervous systems. The gastrointestinal peptides glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP), released from the intestine during oral intake, have been found to play a significant role in augmenting insulin release, an effect known as the incretin effect. When assessing the effect of all these different secretagogues on β‐cell function, it is important to take into account the prevailing insulin sensitivity, as variations in insulin sensitivity lead to compensatory changes in insulin release. Understanding the dynamics and complex regulation of normal insulin secretion in humans provides the basis for understanding the consequences of β‐cell dysfunction observed in diabetes.

Feline Diabetes Mellitus

“…The autonomous nervous system modulates islet hormone release; secretion of insulin is stimulated by vagal nerve fibers and inhibited by sympathetic nerve fibers. Several other pancreatic and extra-pancreatic hormones, such as IAPP, glucagon, somatostatin, cortisol, and growth hormone (GH), affect insulin secretion directly or indirectly (Flatt, 2003;Persaud and Howell, 2003;Utzschneider et al, 2004).…”

Islet cell function: α and β cells - partners towards normoglycaemia

“…β‐cell function is regulated by numerous nutrient, neural and hormonal factors that act to stimulate or inhibit insulin production (Table 1) (7,8); glucose, glucagon and the incretin hormones, such as GLP‐1 and glucose‐dependent insulinotropic polypeptide (GIP), play major roles in this regard. Under normal conditions, insulin secretion from the β cell occurs in a glucose‐dependent manner – this relationship is maintained even when glucose levels exceed physiological levels.…”