In regards to metformin, most common treatment for type 2 diabetes, how do this
ID: 3477274 • Letter: I
Question
In regards to metformin, most common treatment for type 2 diabetes, how do this pharmaceutical strategy work.
Does it attempt to target insulin secretion or insulin sensitivity?
Which receptor, channel, transporter or intracellular factor will be targeted and will it be activated or inhibited?
Explain how targeting this receptor or other factor lead to altered insulin secretion or insulin sensitivity?
Explain how this targeting will lead to improved blood glucose homeostasis.
By considering the action of your targeting at basal glucose, between meals, could there be a risk of hypoglycemia? Describe why?
Explanation / Answer
Answer
Diabetes Mellitus (DM) is a metabolic disorder characterized by the increased level of blood glucose accompanied by greater or lesser impairment in the metabolism of carbohydrate and lipids.and proteins.
Types of Diabetes Mellitus
Diabetes is mainly of two types and other specific types.
1. Type I diabetes
2. Type II Diabetes
Type I Diabetes is also called as insulin dependent diabetes mellitus(IDDM).It is mainly caused by destruction of beta cells islets of Langarhence of pancreas.The destuction is caused by Autoimmune system or idiopathic. So in this condition there no sufficient insulin.
Type II diabetes also called as Non insulin dependent diabetes(NIDDM)., here the production of insulin is there but the insulin is not utilized by the cell due to the insulin resistnce. It is associated with a family history of diabetes, older age, obesity and lack of exercise.
Metformin is the one of most common drug used in tratment of Type II Diabetes. This act by improving the sensitivity of body tissues to the insulin, that leads to increased uptake of glucose and decreases the blood glucose levels. Metformin act by decreaseing hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing glucose uptake and utilization of cells.
The receptor , channels , and transpoters involved are
The improvement in insulin sensitivity by metformin could be ascribed to its positive effects on insulin receptor expression and tyrosine kinase activity.
Metformin act by acutely increases plasma levels of GLP-1 (glucagon-like peptide-1) and increases pancreatic islet incretin receptor gene expression through PPAR (peroxisome-proliferator-activated receptor)-.
The major function of metformin is to decrease hepatic glucose production mainly by inhibiting gluconeogenesis.
The prefererable action of metformini is in hepatocytes is due to the predominant expression of OCT1 (organic cation transporter 1), which provide cellular uptake of metformin.
activated AMPK (AMP-activated protein kinase) is associated with the pleiotropic actions of metformin.
By following mechanisms metformin produces insulin sensitivity
i. The improvement in insulin sensitivity by metformin is positive effects on insulin receptor expression and tyrosine kinase activity. Metformin also beneficial for metabolic actions in part through the modulation of the incretin axis. It induces islet incretin receptor gene expression through a mechanism that is dependent on PPAR (peroxisome-proliferator-activated receptor)-.
It act by inhibiting Gluconeogenesis
Metformin decreases blood glucose level by inhibiting hepatocyte gluconeogenesis,includes modifications in enzyme acivities and gluconeogenic substrates..It causes the prevalent expression of OCT1 (organic cation transporter 1), to facilitate cellular uptake of metformin.
AMPK is a serine/threonine protein kinase.Its role is in protecting cellular functions under energy restricted conditions. AMPK actvated by phosphorylation. Activated AMPK switches cells from an anabolic to a catabolic state, This regulation involves phosphorylation by AMPK of key metabolic enzymes and transcription factors undergoes modulating gene expression. that results iniinhibtion of glucose, lipid and protein synthesis.
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