403- What is glucose–glucagon axis?
In physiology, declining glucose levels result in stimulation of glucagon secre-
tion, whereas rising glucose levels lead to suppression of glucagon secretion.
This tightly regulated phenomenon responsible for the maintenance of glucose
homeostasis may be referred as “glucose–glucagon axis.” The key regulators
involved in this axis include intra-islet insulin, glucose per se, GLP1, GIP, intra-
islet autonomic nervous system, and possibly preserved insulin sensitivity to
α-cell. Decrease in intra-islet insulin due to declining level of glucose acts as a
stimulus to increase glucagon secretion (insulin switch-off signal). In addition,
glucose can directly regulate glucagon secretion, and this effect is modulated
by its effect on KAT P channel present on α-cell membrane through its entry via
GLUT1. GLP1 inhibits glucagon secretion, and this effect is possibly mediated
through increase in intra-islet insulin or due to the direct inhibitory effect of
GLP1 on α-cell or by promoting somatostatin secretion from δ-cell (which in
turn inhibits α-cell). GIP stimulates glucagon secretion and plays a protective
role during hypoglycemia. Intact intra-islet autonomic nervous system and pre-
served insulin sensitivity to α-cell also determine the glucagon response to
glucose.- What is entero-insular axis?
Entero–insular axis or “incretin–β-cell axis” encompasses secretion of insulin
triggered by release of peptides from enteroendocrine cells (incretins) in response
to oral administration of nutrients. The concept of entero–insular axis evolved
after the demonstration of greater insulin response to oral glucose load as com-
pared to intravenous glucose load. This phenomenon was attributed to release of
peptides from enteroendocrine cells in response to glucose. These peptides were
named as incretins and include glucagon-like peptide 1 (GLP1) and glucose-
dependent insulinotropic peptide (GIP). GLP1 is secreted from L-cells present in
the distal ileum and colon, whereas GIP is from K-cells present in the duodenum
and jejunum. Incretin-mediated insulin secretion contributes to 60–70 % of pran-
dial insulin secretion. Both the incretins are rapidly degraded in circulation by an
enzyme called dipeptidyl-peptidase 4 present in endothelial cells.- How do islet cells cross-talk with each other?
Circulating level of glucose is the key determinant for normal functioning of
β-cell and α-cell. In addition, there is an intra-islet periportal circulation which
facilitates cross-talk among different islet cells in a paracrine manner. In
response to rising glucose level, increase in intra-islet insulin inhibits α-cell
(insulin switch-on signal), whereas in response to hypoglycemia reduction in
intra-islet insulin stimulates the α-cell to secrete glucagon (insulin switch-off
signal). Somatostatin secreted from δ-cell has inhibitory effects on both α- and
β-cells. During recovery from hypoglycemia, somatostatin prevents rebound12 Diabetes in the Young