Diabetes mellitus is a metabolic disorder characterized by hyperglycaemia, glycosuria, hyperlipidemia, negative nitrogen balance, and ketonaemia.
Oral Hypogylcaemic Drugs
Diabetes
mellitus is a metabolic disorder characterized by hyperglycaemia, glycosuria,
hyperlipidemia, negative nitrogen balance, and ketonaemia. Most patients can be
classified, clinically, as having either type I diabetes mellitus (insulin
dependent diabetes mellitus (IDDM) or type II noninsulin dependent diabetes
mellitus (NIDDM). The incidence of each type of diabetes varies widely
throughout the world. In the United States, about 5% to 10% of the diabetic
patients have type I diabetes mellitus, with an incidence of 17 per 100,000
found in United Kingdom. The vast majority of diabetic patients have type II
diabetes mellitus.
Type I
diabetes is also called juvenile onset diabetes mellitus. There is β-cell
destruction in the pancreatic islets of langerhans. Majority of the cases are
due to autoimmune (type I A) antibodies that destroy β cells, are detectable in blood,
but some are idiopathic (type I B) no β (beta) cell antibody is found. In all
type I cases, circulating insulin levels are low or
very low and ketosis may occur. Genetic predisposition is also a cause for this
condition.
Type II
diabetes is also called maturity onset diabetes mellitus. There is no loss or
moderate reduction in the β cell mass, insulin in circulation levels is low and
generally has a late onset of disease after middle age. This may be due to an
abnormality in the glucoreceptors of β cells, therefore, they respond at higher
glucose concentrations or at relative β cell deficiency. The reduced sensitivity
of peripheral tissues to insulin and reduction in the number of insulin
receptors are a consequence for producing diabetes. When glucagons exceed a
normal amount, it produces hypoglycaemia. The insulin is secreted by the β cells
of langerhans, synthesized by a single chain precursor of 110 amino acid
preproinsulin. After translocation through the membrane of rough endoplasmic
reticulum, the 24 amino acid N-terminal
peptide of preproinsulin is rapidly cleared off to form proinsulin. Here, the
molecules folds and the disulphide bonds are formed. In the conversion of proinsulin to
insulin in the Golgi complex, four basic amino acids and the remaining
connector or C peptide are removed by proteolysis. This gives rise to two
peptide chains (A and B) of insulin molecules, which contains one intrasubunit
and two intersubunits disulphide bonds. The A chain consists of 21 amino acids
and B with 30 amino acids and molecular mass is about 5734 daltons.
The
regulatory factors of insulin secretion are chemical, hormonal, and neural.
Chemical regulation depends upon the glucose entry in to the β cells by glucose
transport. Once, after the entry of glucose and its phosphorylation by
glucokinase, glucoreceptor activation indirectly inhibits the adenosine triphosphate (ATP) sensitive potassium channels and increases
intracellular calcium, which triggers the exocytic release of insulin. Hormonal
change in corticosteroids modify the release of insulin. Insulin inhibits
glucagon secretion and glucagons increase the insulin secretion.
The neural
control is mediated by α2 and β2 receptors. Stimulation
of α2 receptor decreases the insulin release and stimulation of β2
receptors increases insulin release. Cholinergic stimulation increases the
insulin secretion.
Hypoglycaemic
drugs are agents, which decrease the blood sugar level. Oral hypoglycaemic
agents must be distinguished from more hypoglycaemic drugs, such as
salicylates, which are too toxic for clinical use in doses that effectively
lower the blood sugar. An ideal antidiabetic drug should be nontoxic and
correct the basic metabolic defects in diabetics, in addition to lowering the
blood sugar.
Related Topics
TH 2019 - 2024 pharmacy180.com; Developed by Therithal info.