6.1 Glucose Homeostasis

JCU Pharmacy

6.1 Glucose Homeostasis

Learning Outcomes

Be able to:

Describe the physiological role of insulin, glucagon and other counter regulatory hormones in glucose homeostasis.

Introduction to Glucose Homeostasis

The regulation of blood glucose levels is complex. The body regulates blood glucose levels to balance having enough cellular energy available for cells to function against having too much blood glucose for too long. The body tries to regulate blood glucose somewhere between 4.0 and 7.8mmol/L. Blood glucose levels below 4.0mmol/L causes hypoglycemia, which is a potentially life threatening state. Conversely, sustained hyperglycaemia damages small and large blood vessels and can lead to retinopathy, nephropathy and neuropathy. We will now discuss the two major organs involved in the regulation of blood glucose levels, the pancreas and liver.

The pancreas

The pancreas performs a variety of exocrine and endocrine functions. This week we will focus on the endocrine function of the pancreas, which involves the regulation of blood glucose levels. Insulin and glucagon are both peptide hormones produced by cells found in the islets of Langerhans in the pancreas. Insulin is produced in the beta cells while glucagon is produced in the alpha cells. Locate the depiction of these cells using the image below.

Insulin and glucagon have opposing effects on blood glucose levels and are released in response to differing physiological states. Insulin LOWERS blood glucose in the fed state while glucagon RAISES blood glucose levels in the fasting state.

📺Watch the following video: An introduction to the role of the pancreas in glucose regulation. (1:38 min.)

The liver

After meals, glucose is stored as glycogen in the liver. During fasting periods, glucose is released from glycogen and made available to other tissues. The function of the liver is influenced by a number of hormones, including insulin and counter regulatory hormones. We will discuss these hormones next.

📺Watch the following video on the role of the liver in regulating blood glucose levels. (2:02 min.)

Before we discuss insulin and counter regulatory hormones like glucagon, review the image below to solidify your understanding of the role of the pancreas and liver in glucose homeostasis.

Insulin, Glucagon and the Other Counter Regulatory Hormones

Insulin

Insulin is released in the fed state in response to elevated blood glucose levels. When insulin binds to the insulin receptor (a tyrosine kinase receptor) on the cell membrane it triggers a variety of important cellular processes including:

Increased expression of glucose transporters (GLUT4) on the cell wall which allow glucose to move across the cell membrane into muscle and adipose cells.
Increase energy storage:
- Increased glycogen synthesis (glycogenesis)
- Fat synthesis (lipogenesis)
Inhibit lipid and protein breakdown (lipolysis and proteolysis)
Inhibit ketogenesis:
- Inhibit free fatty acid formation (occurs during lipolysis)
- Prevent free fatty acids entering mitochondria where they can be metabolised to ketoacids
Inhibit glucagon production in alpha cells.

📺 Watch this YouTube video to help review insulin

Glucagon

Glucagon is only one of several counter-regulatory hormones. Glucagon is released from alpha cells in response to hypoglycaemia. In the clinical context, an understanding of glucagon’s actions is vital to understanding the management of hypoglycaemia and why diabetic ketoacidosis occurs.

Hypoglycaemia:
- Glucagon triggers hepatic glucose production by converting glycogen stores into glucose (glycogenolysis). This hepatic glucose production leads to increased BGLs, correcting the hypoglycaemia.
Hyperglycaemia:
- Elevated blood glucose levels and subsequent insulin release from beta cells reduce glucagon release from alpha cells. Reduced glucagon release leads to lower hepatic glucose production, helping to prevent further elevation of BGL.
Diabetic ketoacidosis:
- In diabetes, there is a lack of insulin. The lack of insulin limits the negative feedback on glucagon release that normally occurs. The ‘unopposed’ glucagon release from alpha cells is therefore able to drive catabolic processes including lipolysis which produces free fatty acids that can ultimately be converted into keto acids.

📺 Watch this YouTube video to help review glucagon

Other counter regulatory hormones

The other counter regulatory hormones include:

Adrenaline
Cortisol
Somatostatin.

Adrenaline, released from the adrenal cortex in response to stimulation of the sympathetic pathway of the autonomic nervous system increases blood glucose levels rapidly by stimulating glycogenolysis and gluconeogenesis in the liver. Cortisol is also released from the adrenal cortex and stimulates the hepatic production of glucose from proteins and lipids, inhibits insulin release, promotes glucagon release, decreases muscle uptake of glucose and stimulates the production of glucose from adipose tissue. The response of cortisol is slower (hours) and represents a longer term response to the homeostatic control of blood glucose levels.The final two final counter regulatory hormones are somatostatin and growth hormone. These are less important but do play a role in glucose homeostasis. Somatostatin is released by Delta cells in pancreatic islet cells and inhibits secretion of insulin and glucagon as well as slowing absorption of nutrients from the gastrointestinal tract. Growth hormone counteracts the general effects of insulin in terms of glucose production and lipid metabolism. It also has an anabolic effect (similar to insulin) on tissues.

There is a close relationship between insulin, glucagon and other counter-regulatory pathways that work to maintain ‘normal’ blood glucose levels and a constant supply of energy to cells throughout the day. A disruption in insulin leads to dysfunction throughout the associated pathways. The image below shows the interconnectedness of feedback loops at play in BGL regulation.

📺Watch the following lecture video: an introduction to insulin and the counter regulatory hormones – Part 1 (6:58 min.)

📺Watch the following video: an introduction to insulin and the counter regulatory hormones – Part 2 (8:27 min.)

Check your understanding:

COMMONWEALTH OF AUSTRALIA Copyright Regulations 1969 WARNING

This material has been reproduced and communicated to you by or on behalf of James Cook University in accordance with section 113P of the Copyright Act 1969 (Act).

The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice.