Clinical Quick Reference Monthly Newsletter / June 2022 / Incretins & T2D
Clinical Quick Reference Guides - Clinical Concept Review/ Incretins & T2D
This review will help clarify the incretins, pancreatic endocrine hormones, and T2D.
What are Incretins?
Incretins are metabolic hormones (protein hormones) that can affect glucose metabolism and decrease blood glucose levels. This modulation is related to their ability to stimulate release of insulin by β cells while inhibiting the release of glucagon by pancreatic α cells.
β cells, α cells --- What's Going On In the Pancreas?
The human pancreas is an organ that has both exocrine and endocrine functionality; it is a part of the digestive system and the endocrine system. It is located in the abdomen, where it stretches from behind the stomach to the left upper abdomen.
The pancreas is divided into the head region, neck, body, and tail portion. The majority of pancreatic function is exocrine. Only a small percentage of its functioning is endocrine (sometimes estimated to be as low as 1%).
Its endocrine portion is arranged as discrete islets of Langerhans.
The Islets of Langerhans are groupings of pancreatic cells, first noted by Dr. Paul Langerhans, a pathologist (1869). [NIH]
Islet cells include five different endocrine cell types (alpha, beta, delta, epsilon, and upsilon). They secrete at least five distinct hormones: glucagon, insulin, somatostatin, ghrelin, and pancreatic polypeptide.
β (beta) cells comprise the majority of the islet mass (60%). α (alpha) cells comprise approximately 30% of islet mass.
The Pancreatic Endocrine Cells and Their Hormones
This is a good opportunity to reflect on the various pancreatic endocrine cells and their hormones. Feel free to grab notebook, sticky notes or tablet. Jotting things down will make them easier to remember.
The pancreatic endocrine cells include:
alpha cells
release glucagon
beta cells
release insulin
delta cells
release somatostatin
epsilon cells
release ghrelin
PP cells
release pancreatic polypeptide
Note: These cells can influence the release of hormones by one another.
T2D (Diabetes Mellitus Type 2)
T2D, Hyperglycemia and Blood Glucose Modulation
T2D, or Diabetes mellitus Type 2, is a chronic metabolic disorder. T2D is characterized by persistent blood sugar elevations (hyperglycemia). This may occur as a result of impaired insulin secretion, peripheral resistance to the action of insulin, or both.
Symptoms of hyperglycemia tend to develop slowly; usually over several days or weeks. The longer blood sugar levels are elevated, the more serious the symptoms become. The condition is most often linked with diabetes.
*Insulin secretion in the pancreas occurs in the beta cells (β).
📌 β cells release insulin, the peptide hormone that in turn acts to decrease glucose levels in the blood
Now, back to the incretins. Remember that the incretins are types of protein hormones that can function to modulate glucose metabolism by stimulating the release of insulin by the β cells and inhibiting glucagon release by pancreatic α cells.
But, where are these incretins coming from?
Incretins are gut peptides. Simply put, incretins arise from the gastrointestinal tract. Ingested nutrients trigger their release [CDC, NIH] which subsequently initiates the secretiom of insulin by β cells. This insulin secretory response is referred to as the “incretin effect.”
The incretin effect accounts for at approximately half of the total insulin released after oral glucose intake.
GIP, “glucose-dependent insulinotropic polypeptide,” and GLP-1, “glucagon-like peptide-1,” are the incretins responsible for the incretin effect. It is important to note that in patients with T2D, the incretin effect may be diminished or absent.
To review: after a person eats, the gut releases hormones.
Two of the key ones are the incretins— GLP-1 and GIP.
GLP-1 also works to decrease glucagon release at meals, helping to further modulate blood sugar.
It is important to understand that the incretins do not function unchecked. Shortly after being released, they are quickly broken down by an enzyme known as DPP-4.
Incretins and Blood Sugar Management in T2D
After reviewing the incretins and their effects, it is not surprising to note that incretin‐based therapies have emerged as key therapeutics in the treatment of T2D.
Incretin-based therapeutics produce effects via the incretin system. The key mechanism of action specifically targets a receptor for the incretin hormone glucagon‐like peptide 1 (GLP‐1). [NIH]
Treatments for T2D affecting this incretin system include: DPP-4 inhibitors (oral medications for patients with T2D) and GLP- 1 analogs (injected medications for patients with T2D).
DPP-4 Inhibitors
block DPP-4 from breaking down GLP-1 as quickly
helps control blood sugar levels, especially after eating
GLP- 1 analogs
are injected medicines (T2D)
developed to resist breakdown that occurs via DPP-4
medicine lasts longer in the blood stream, lengthens time of GLP- 1 similar activities
Medical Terminology
Getting to know these terms will help reinforce the above material.
endocrine – to secrete internally; internal secretions are transported around the body by the bloodstream; endocrine system consists of organs and glands throughout the body that make, store, and secrete chemical messengers (hormones)
enzyme – biological catalysts; almost always proteins; speed up the rate of specific chemical reactions in cells
exocrine – to secrete externally; secretes substances through ducts; exocrine system includes a series of glands all over the body that secrete substances including sweat, breast milk, mucus and oil
glucose - monosaccharide sugar (C₆H₁₂O₆); used by living things to obtain energy through the process of aerobic respiration
incretins - group of hormones that stimulate a decrease in blood glucose levels
insulin - peptide hormone produced by beta cells of the pancreatic islets, activity helps lower blood glucose levels
Anatomy & Physiology
Becoming familiar with these body systems will help increase understanding of body processes and medical conditions
pancreas
glandular organ
located in the upper abdomen
functions as two glands in one a digestive exocrine gland and a hormone-producing endocrine gland
Exocrine gland function: secretes enzymes to break down the proteins, lipids, carbohydrates, and nucleic acids in food
Endocrine gland function: secretes hormones, for example: insulin and glucagon, that help to control blood sugar levels throughout the day
Helpful video:
Disclaimer: The above study guide represents study materials, always seek and follow the advice of your medical provider for any acute or chronic medical issues or questions.