Heterogeneous effects of inhibitors of receptor processing on insulin binding and intracellular accumulation in various cell types. 1986

R M Smith, and T S Gansler, and N H Laudenslager, and N Shah, and L Jarett

This study utilized uniform incubation conditions and demonstrated heterogeneity in the effects of various agents on 125-insulin binding and intracellular accumulation in five cell types. The cells used in this study included rat adipocytes, H4IIEC3 cultured hepatoma cells, normal human fibroblasts, and 3T3-L1 preadipocytes and adipocytes. Bacitracin increased insulin binding to rat adipocytes but inhibited binding to all other cells. Chloroquine increased total cell-associated insulin in all cells except H4IIEC3 hepatoma cells. Methylamine and dansylcadaverine increased or decreased binding depending on cell type. Similar heterogeneity was found in the intracellular accumulation of insulin. Under control conditions, intracellular insulin at steady state varied from 16 to 52% of the total cell-associated insulin. Bacitracin decreased intracellular accumulation of insulin in 3T3-L1 adipocytes, preadipocytes, and human fibroblasts but increased accumulation in rat adipocytes. Chloroquine increased insulin accumulation in all cell types except H411EC3 hepatoma cells. Both methylamine and dansylcadaverine increased intracellular insulin in rat adipocytes and decreased accumulation in human fibroblasts. These results provide additional evidence of heterogeneity in insulin and/or insulin receptor processing among different cell types.

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
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008744 Methylamines Derivatives of methylamine (the structural formula CH3NH2).
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
D002103 Cadaverine A foul-smelling diamine formed by bacterial DECARBOXYLATION of LYSINE. It is also an intermediate secondary metabolite in lysine-derived alkaloid biosynthetic pathways (e.g., QUINOLIZIDINES and LYCOPODIUM). 1,5-Pentanediamine,BioDex 1,Pentamethylenediamine,1,5 Pentanediamine
D002738 Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Aralen,Arechine,Arequin,Chingamin,Chlorochin,Chloroquine Sulfate,Chloroquine Sulphate,Khingamin,Nivaquine,Sulfate, Chloroquine,Sulphate, Chloroquine
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
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

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