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Diabetes and Obesity Antibodies

A very extensive range of antibodies to proteins associated with diabetes and obesity.

The gut is the largest endocrine organ producing numerous peptide hormones with various functions ranging from regulating gastic motility and insulin release to regulating appetite.

Glucagon-like-peptide 1 (GLP-1) has been of particular interest in both obesity and diabetes research as it is released by the intestine in response to food and stimulates secretion of insulin.

Receptors for this peptide are also located in the brain in regions associated with appetite and feeding behaviour. This has also lead to the study of GLP-1 analogues such as Exendin-4 which occurs in the venom of the Glia monster which may potentially be of use in anti-obesity therapy.

Obesity is a major risk factor for development of Type II diabetes as such there is much interest in the gut hormones that regulate appetite.

Glucagon-like peptide 1 (GLP-1) is released by the small intestine in response to nutrients in the gut lumen. GLP-1 regulates glucose levels by stimulating glucose-dependent insulin secretion and suppressing glucagon secretion and promotes satiety by delaying gastric emptying.

Peptide YY (PYY), like GLP-1 is a member of the pancreatic peptide (PP) family and also inhibits gastric secretion and gastric emptying. As such, the potential use of analogues of these hormones as therapeutic agents continues to be an area of interest.

Diabetes Mellitus is a group of metabolic disorders which result in elevated blood sugar resulting in symptoms of increased urination, increased thirst and increases hunger. The Quality and Outcomes Framework data for 2011 reports that on average 4.45% of the UK population are diagnosed as diabetic and it is estimated that around 10% of the NHS budget is spent on the treatment of diabetes and associated complications.  Given the prevalence of this disorder and an increasing trend is it not surprising that diabetes research is a key focus area.  A four year investment plan was announced in 2011 by the government to spend £800 million on translational research to improve care and treatment of patients with diseases such as cancer, diabetes and heart disease and the charity Diabetes UK aims to invest £6 million in diabetes research during 2012.

Diabetes is divided into 3 main types but other forms such as congenital and monogenic also exist. 

  1. Type I Diabetes - Aka juvenile diabetes or insulin dependent diabetes mellitus (IDDM) where the insulin producing cells have been destroyed and the body cannot produce insulin
  2. Type II Diabetes - Aka adult onset or non-insulin dependent diabetes mellitus (NIDDM), where the body’s cells fail to respond properly to insulin – insulin resistance which may also be coupled with insulin insufficiency.
  3. Gestational Diabetes - This affects pregnant women who have never had diabetes before but suffer elevated blood glucose during pregnancy and resembles Type II diabetes.

Regulating Glucose

Two hormones, glucagon and insulin, serve to regulate blood glucose and play an important part in carbohydrate metabolism.   In non-diabetic individuals when blood glucose is low the pancreas will release glucagon which prompts the liver to convert stored glycogen into glucose for release into the blood stream, a process known as gluconeogenesis.  Conversely when blood sugar rises the pancreas releases insulin which instructs the body to store glucose.  Together these two hormones operate as a corrective mechanism to keep a stable blood glucose concentration. 

Ketoacidosis

In diabetes patients loose the ability to strictly control blood glucose levels.  The lack of insulin/insulin resistance fails to trigger the corrective glycogen production and storage mechanism in response to elevated blood glucose.  In Type I diabetes (and Type II in certain circumstances) the insulin insufficiency will result in increased release of glucose from the liver driving blood sugar even higher.  Whilst glucose is the body’s preferred source of energy when this is not available the body will switch to fatty acid metabolism instead. Fat metabolism produces ketones, acidic molecules which can build up in the blood and lead to ketoacidosis. 

Diagnostic Tests

Blood and urine glucose and serum ketone bodies tests may be used to aid diagnosis of diabetes and also when monitoring a disease management effectiveness.  Glycated serum proteins are also a valuable tool for assessing the effectiveness of a treatment and compliance to a prescribed regime.  When glucose levels in the blood remain elevated over a period of time the glucose will permanently combine with protein and haemoglobin molecules – resulting in glycated serum proteins and glycated haemoglobin.  Measuring these glycated molecules gives information on how well blood glucose has been controlled as the greater the level of glucose in the blood the more glycated proteins will be formed. One such test measures fructosamine, which is formed when the carbonyl group of glucose reacts with the amino group of a protein.

Diabetes Management

Different foods affect blood sugar differently and therefore diet is important in diabetes management.  What to eat, and when, are important factors for type I patients to ensure the amount of glucose released for the insulin that has been taken.   In most cases type I diabetes will require regular insulin injections or an insulin pump and close blood glucose monitoring. 

Lifestyle changes are a first line approach when tackling type II diabetes, carefully planned diet and exercise may be enough to keep blood glucose at a healthy level for some individuals.  As the disease progresses additional medication to reduce high blood sugar may be introduced such as metformin and sulphonylureas.  In some cases patients may require insulin injections.  Treatments such as sulphonylureas and insulin may have unwanted side effects for some individuals including weight gain.

Individuals with Diabetes are at increased risk of cardiovascular disease, stroke and kidney problems.  As suchcholesterol levels may be monitored periodically and elevated levels require treatment with statins.  Phospholipidsand Non-esterified fatty acids may also be predictive indicators of type II diabetes risk.

High blood glucose can damage vessels in the kidney, eyes and nerves and regular examinations of the eyes and feet are also recommended.

Appetite and Satiety Research

Obesity is a major risk factor for development of Type II diabetes as such there is much interest in the gut hormones that regulate appetite.  Glucagon-like peptide 1 (GLP-1) is released by the small intestine in response to nutrients in the gut lumen. GLP-1 regulates glucose levels by stimulating glucose-dependent insulin secretion and suppressing glucagon secretion and promotes satiety by delaying gastric emptying.  Peptide YY (PYY), like GLP-1 is a member of the pancreatic peptide (PP) family and also inhibits gastric secretion and gastric emptying. As such, the potential use of analogues of these hormones as therapeutic agents continues to be an area of interest.

 

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