Biomaterial Database

The effects of metabolic acidosis in vivo on insulin binding to isolated rat adipocytes. 1982

J Whittaker, and C Cuthbert, and V A Hammond, and K G Alberti

Insulin resistance in vivo and impaired insulin binding to isolated adipocytes are characteristic of diabetic ketoacidosis in the rat. To determine the respective roles of diabetes and acidaemia in the genesis of the binding defect, insulin binding to adipocytes from alkali-treated ketoacidotic diabetic and ammonium chloride acidotic rats was studied. Reversal of the acidaemia of ketoacidotic rats by sodium bicarbonate infusion (pH 6.73 +/- 0.027 to 7.35 +/- 0.027, p less than 0.001, n = 12) increased adipocyte insulin binding (0.51 +/- 0.21% to 2 x 10(5) cells/ml, n = 6 untreated versus 1.10 +/- 0.27% to 2 x 10(5) cell, n = 6 treated, p less than 0.05). Scatchard analysis showed this to be due to an increase in insulin receptor concentration. Ammonium chloride infusion caused marked metabolic acidaemia (pH 6.72 +/- 0.04, n = 12) and insulin binding to adipocytes was markedly decreased (0.81 +/- 0.12% to 2 x 10(5) cells/ml n = 6 versus 2.40 +/- 0.22% to 2 x 10(5) cells/ml, n = 6 in controls p less than 0.02), due to a change in receptor concentration. The apparent affinity of the receptor was markedly decreased in diabetic animals compared with normal controls but was unchanged in ammonium chloride acidotic animals. Thus in diabetic ketoacidosis there is both decreased affinity and number of insulin receptors partially reversible by prolonged alkali infusion. Only changes in affinity appeared to be specific for the diabetic state.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008297	Male		Males
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011972	Receptor, Insulin	A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.	Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D000138	Acidosis	A pathologic condition of acid accumulation or depletion of base in the body. The two main types are RESPIRATORY ACIDOSIS and metabolic acidosis, due to metabolic acid build up.	Metabolic Acidosis,Acidoses,Acidoses, Metabolic,Acidosis, Metabolic,Metabolic Acidoses
D000273	Adipose Tissue	Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.	Fatty Tissue,Body Fat,Fat Pad,Fat Pads,Pad, Fat,Pads, Fat,Tissue, Adipose,Tissue, Fatty
D000643	Ammonium Chloride	An acidifying agent that has expectorant and diuretic effects. Also used in etching and batteries and as a flux in electroplating.	Sal Ammoniac,Ammoniac, Sal,Chloride, Ammonium
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001639	Bicarbonates	Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the pH of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.	Bicarbonate,Bicarbonate Ions,Hydrogen Carbonates,Bicarbonate Ion,Carbonic Acid Ions,Hydrogen Carbonate,Carbonate, Hydrogen,Carbonates, Hydrogen,Ion, Bicarbonate,Ions, Bicarbonate,Ions, Carbonic Acid
D001667	Binding, Competitive	The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.	Competitive Binding