hormones and type 1 diabetes

Posted on 26 July 2009

Another repost from my old website. Hope you find it interesting!

Insulin

In the interest of getting a better understanding of the endocrinology behind diabetes, I decided this afternoon to have a poke around the web at information on hormonal glucose regulation.

Type 1 diabetes is fundamentally a disorder of glucose regulation related to the body’s inability to produce insulin. The cells of the body that produce insulin are located in the pancreas in the regions known as the “islets of Langerhans” [2]. In type-1 diabetes, these insulin-producing cells (beta-cells) are destroyed due to an autoimmune response resulting in a dramatic reduction or elimination of the body’s production of insulin.

Since there are a number of glucoregulatory hormones which increase blood glucose levels (including one produced in alpha-cells of the pancreas called glucagon), the absence of insulin leads to a state of hyperglycaemia if untreated. Chronically high levels of glucose in the bloodstream can lead to a number of complications. A lack of insulin in the bloodstream can also lead to diabetic ketoacidosis. Ketoacidosis means the pH level of the blood falls below its normal range due to the acidic effect of ketone bodies in the bloodstream. The reason for the presence of ketone bodies in the bloodstream is related to the body’s mechanisms for handling starvation.A human body requires an energy source for body metabolism. In particular, the brain requires glucose as its energy source and is unable to perform direct uptake of free fatty acids (FFAs) for use in metabolism. It also always requires glucose as an energy source. In a human undergoing starvation, insulin levels in the blood fall to low levels. The effect of this is to stimulate lipolysis in adipose tissue as part of a wider mechanism of conserving glucose. Lipolysis is the breakdown of body fat into FFAs in the bloodstream and adipose tissue is fat-storage tissue located around the body. The liver processes these FFAs into “ketone bodies” (actually carboxy acids – acetoacetate and beta-hydroxy butyrate) [5]. Ketone bodies can be used in a 50-50 ratio with glucose by the brain as an energy source. The body must carefully regulate ketone body production during starvation via the insulin:glucagon ratio during starvation as overproduction will overwhelm the blood’s pH buffer capacity resulting in ketoacidosis.

The reason for ketoacidosis in type-1 diabetes is probably becoming a little clearer. In the absence of insulin, lipolysis proceeds at a rapid rate and the liver processes FFAs into ketone bodies. Lipolysis is increased because an insulin-inhibited enzyme called lipase in adipose tissue is active in the absence of insulin. Since there is no mechanism for the body to control the insulin:glucagon ratio and thus regulate lipolysis, ketone body generation soon overcomes the blood’s pH buffer and the pH begins to fall. Ketoacidosis can lead to coma and death through disruption to metabolism.

What are the hormonal causes of hyperglycaemia experienced in untreated type-1 diabetes? I mentioned early on that there are a number of glucoregulatory hormones which cause an increase in blood glucose levels. Hormones don’t just act as activating agents though, they also act as inhibitory agents. We saw this in the example of the increased rate of lipolysis without insulin. Insulin also acts as an inhibitory agent for hepatic gluconeogenesis – the production of glucose from a substrate in the liver. Even though blood glucose concentrations are already high, the lack of insulin in the blood causes the body to break down muscle protein, convert it to alanine and send it to the liver for gluconeogenesis, further increasing blood glucose concentration [7]. Generally most other complications from diabetes are related to the flow-on effects of hyperglycaemia.

I think that’s about all the scientific jargon I can take for today. For more reading about glucoregulatory hormones, check out my first reference. It’s quite dense on the biochemical jargon. Feel free to post a comment if you want anything translated – I did study two years of biochemistry after all – might as well use it!

[1] http://spectrum.diabetesjournals.org/cgi/content/full/17/3/183 (Very useful)
[2] http://web.indstate.edu/thcme/mwking/diabetes.html
[3] http://en.wikipedia.org/wiki/Diabetes_mellitus_type_1
[4] http://en.wikipedia.org/wiki/Diabetic_ketoacidosis
[5] http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm (Very useful)
[6] http://en.wikipedia.org/wiki/Acidosis
[7] http://web.indstate.edu/thcme/mwking/gluconeogenesis.html


2 responses to hormones and type 1 diabetes

  • Testosterone Dude! says:

    OK, I enjoyed your post, but I do have a translation request. Not from your reference, but from your article….

    I followed you just fine until we got to this…

    Hormones don’t just act as activating agents though, they also act as inhibitory agents. We saw this in the example of the increased rate of lipolysis without insulin. Insulin also acts as an inhibitory agent for hepatic gluconeogenesis – the production of glucose from a substrate in the liver.

    Could you elaborate?

    Thanks much!

    • cam says:

      Basically, the presence of a hormone can either boost some kind of activity, or reduce some kind of activity. In this case, the presence of insulin serves to reduce the amount of glucose which is made by the liver. This is really important as it means that even without consuming glucose, blood sugar levels will still tend to rise due to the body’s own production of glucose from (mostly) glycogen, and later due to synthesis of glucose from various other substrates including amino acids.

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