Eczema is not just skin-deep; the disease can have a serious impact on patients' quality of life and overall health, both physically and mentally, according to an expert. Type 2 diabetes can be due to increased peripheral resistance to insulin or to reduced secretion of insulin. Glucose is then stored as glycogen in liver and muscle.Insulin also inhibits the release of glucagon and so blocks fat being used as an energy source. There are one million to three million islets of Langerhans (pancreatic islets) and beta cells constitute 60-80% of all the cells.
Insulin is synthesised from the proinsulin precursor molecule by the action of proteolytic enzymes, known as prohormone convertases, as well as the exoprotease carboxypeptidase E.
There are a family of four specialised transporter proteins that carry glucose across the membrane. GLUT4 carries glucose into muscle and adipose tissue after the insulin receptor has been stimulated - see diagram above.
This treats insulin resistance.Sulfonylureas (gliclazide) bind to an ATP-dependent potassium channel on the cell membrane of pancreatic beta cells. This depolarisation opens voltage-gated calcium channels which leads to increased fusion of insulin granulae with the cell membrane, and increased secretion of (pro)insulin.Glitazones also treat insulin resistance. They bind to peroxisome proliferator-activated receptor gamma (a nuclear regulatory protein) which influences insulin-sensitive genes, which enhance production of mRNAs of insulin-dependent enzymes. It should be remembered that there is a temporary increased risk of lactic acidosis in situations where increased tissue hypoxia occurs, e.g. This is increased in older age groups, mild-to-moderate hepatic impairment, and renal impairment. The trials that have been done indicate that the incidence of hypoglycaemia is equivalent to that of the older sulphonylureas.18ThiazolidinedionesThiazolidinediones (TDZs) or 'glitazones' - pioglitazone19 is the only one currently licensed in the UK.
Its mechanism of action is still subject to debate but is thought to act in a similar manner to metformin, increasing hepatic sensitivity to insulin, and enhancing glucose clearance. They also slow the rate of absorption of nutrients into the bloodstream by reducing gastric emptying, and may directly reduce food intake. Both are rapidly deactivated by dipeptydyl peptidase-4 (DPP4) GLP1 is not useful in diabetes treatment, as it has a very short half-life and must be given as a continuous subcutaneous (SC) injection.
Inhibiting the enzyme that inactivates GLP1 is more successful and several oral DPP4 inhibitors are available for type 2 diabetes management, e.g. Updated 3rd November 2008, accessed 29 Dec 2009Klip A, Leiter LA; Cellular mechanism of action of metformin.
Updated September 2005, accessed 29 Dec 2009Landgraf R, Bilo HJ, Muller PG; A comparison of repaglinide and glibenclamide in the treatment of type 2 diabetic patients previously treated with sulphonylureas. Updated 24 Feb 2009, accessed 29 Dec 2009Wada K, Nakajima A, Katayama K, et al; Peroxisome proliferator-activated receptor gamma-mediated regulation of neural stem cell proliferation and differentiation. Updated 10 November 2009, accessed 29 Dec 2009Sitagliptin, New Drug Evaluation No 45, Regional Drug and Therapeutic Centre, (Aug 2007)Summary of Product Characteristics (SPC) - Galvus® 50 mg tablets (vildagliptin), Novartis Pharmaceuticals UK Ltd, electronic Medicines Compendium. Updated Aug 2009, accessed 29 Dec 2009Summary of Product Characteristics (SPC) - Byetta® (exenatide), (5 micrograms and 10 micrograms solution for injection, prefilled pens), Eli Lilly and Company Limited, electronic Medicines Compendium.
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