Other Factors that Stimulate Insulin Secretion

Carbohydrates are not the only factors that will lead to insulin secretion by the beta cells of
the pancreas. The following are other factors that may influence insulin production:

Insulin stimulates the incorporation of amino acids into proteins and combats the fat
catabolism that produces the B-keto acids (Ganong, 2003). Amino acids, particularly arginine and
lysine, have an effect in stimulating insulin production. They generate ATP when metabolized and
close ATP-sensitive potassium channels in the beta cells of the pancreas causing depolarization of
the plasma membrane, opening the calcium channels that results to an influx of calcium ions into
the cell. This results in exocytosis of insulin-containing vesicles. Additionally, nitric oxide (produced in
the islet of Langerhans), of which L-arginine is a precursor, stimulates insulin production. In the
absence of a rise in blood glucose, however, secretion is only very minimal. But, when partnered
with an increase in blood glucose concentration, insulin secretion may be doubled with excess amino
acids. Amino acids strongly potentiate the glucose stimulation for insulin secretion (Hall, 2016).
Insulin secretion by excess amino acids also promote increased transport of these fundamental
protein units into tissue cells.

Gastrointestinal hormones, particularly glucagon-like peptide (GLP-1) and glucose-

dependent insulinotropic peptide (GIP)—collectively known as incretins—enhance the rate of insulin
release from the beta cells of the pancreas as a response to the increase in blood glucose
concentration in the blood. Simultaneously, they also inhibit glucagon release from the alpha cells.
These hormones are released in the gastrointestinal tract as soon as a person eats his meal, causing
an “anticipatory” increase in insulin in order that glucose and amino acids may be readily absorbed
by the cells. Like amino acids, they double the rate of insulin secretion as blood glucose levels rise.
This action explains that orally administered glucose produces a greater production of insulin than
intravenously administered glucose.

Certain hormones also impact the production of insulin. These hormones either directly
increase insulin secretion or potentiate the glucose stimulus for insulin secretion, and they include
the following: glucagon, growth hormone, cortisol, and epinephrine. The importance of the
stimulatory effects of these hormones is that prolonged secretion of any one of them in large
quantities can occasionally lead to exhaustion of the beta cells of the islets of Langerhans and
thereby increase the risk for the development of diabetes mellitus (Hall, 2016).

Glucagon is a hormone secreted by the alpha cells of the islets of Langerhans and serves to
inhibit the production of insulin, resulting to its rise when hypoglycemia sets in so that glycogenesis
in the liver may be stimulated to increase the blood glucose concentration in the blood. Glucagon
and insulin have an inverse relationship to each other: an increase in insulin production results to a
decrease in glucagon production, and vice versa. Simply put, increased blood glucose inhibits
glucagon secretion.

However, the same could not be said when amino acids are involved. Increased amino acids
stimulate the secretion of glucagon. This mechanism proves to be beneficial in further making
glucose available to the cells as glucagon promotes faster conversion of amino acids to glucose.
 The growth hormone is secreted by the anterior pituitary gland, and serves to increase
hepatic glucose output, exerts an ant-insulin effect in muscle, and decrease tissue binding of insulin
(Ganong, 2003). Furthermore, it does not stimulate the pancreas directly but the hyperglycemia it
produces increases the sensitivity of the islets of Langerhands to insulinogenic stimuli, like arginine
and glucose, which may eventually exhaust the beta cells.

Cortisol is called “the stress hormone” and is secreted by the adrenal corticoid complex of
the kidneys and functions similarly with the growth hormone—increasing the blood glucose levels in
the body, but reducing its utilization by the cells.

Epinephrine and norepinephrine, are catecholamines produced by the adrenal medulla, and
are significantly involved in the autonomic nervous system. Their interplay with each other affects
the insulin production in the body. The islets of Langerhans are greatly innervated with sympathetic
and parasympathetic nerves. Stimulation of the sympathetic nerves inhibits insulin production, as a
result of norephinephrine acting on alpha (2) -adrenergic receptors, and instead, increases glucagon
secretion, especially during hypoglycemia. Stimulation through the B-adrenergic receptors, on the
other hand, enhances insulin secretion, such as when the parasympathetic nervous system is
stimulated during hyperglycemic episodes.

References:

Ferrier, D. Lippincott’s Illustrated Reviews: Biochemistry. 6th Edition. Philadelphia, PA: Lippincott
Williams & Wilkins; 2014

Ganong, W. Review of Medical Physiology. 21st Edition. United States of America: McGraw-Hill
Companies, Inc.; 2003

Hall, J. Guyton and Hall Textbook of Medical Physiology. 13th Edition. Philadelphia, PA: Elsevier, Inc.;
2016

Tortora, G. et al. Principles of Anatomy & Physiology. 14th Edition. Milton, Queensland: John Wiley &
Sons Australia, Ltd; 2016