Chronic primary hyperinsulinaemia is associated with altered insulin receptor mRNA splicing in muscle of patients with insulinoma. 1996

P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
Division of Endocrinology 1, Università La Sapienza Rome, Italy.

Alternative splicing of the 36-base pair exon 11 of the human insulin receptor gene results in the synthesis of two insulin receptor isoforms with distinct functional characteristics (the isoform containing exon 11 has lower insulin binding affinity and lower internalization rate). Altered expression of these insulin receptor isoforms has been previously demonstrated in skeletal muscle of patients with non-insulin-dependent diabetes mellitus (NIDDM). However, this observation was not confirmed by other studies and is still a matter of controversy; furthermore, it is not known whether it represents a primary event or is secondary to hyperinsulinaemia and insulin resistance. In order to address this issue in patients with pure non-genetically determined hyperinsulinaemia, we examined the alternative splicing of insulin receptor mRNAs in skeletal muscle of eight patients with surgically confirmed insulinoma and insulin resistance and in eight healthy subjects, using the reverse transcriptase-polymerase chain reaction technique. The insulinoma patients displayed a significant increase in the expression of the insulin receptor isoform containing exon 11 (75.7 +/- 2.3%) when compared with normal subjects (57.9 +/- 1.5%); furthermore, this increase was positively correlated with plasma insulin concentration and negatively correlated with in vivo insulin sensitivity (glucose clamp). In conclusion, the increased expression of the insulin receptor isoform with lower insulin binding affinity in patients with primary non-genetically determined hyperinsulinaemia supports a role for insulin in the regulation of alternative splicing of insulin receptor pre-mRNA and suggests that in NIDDM an altered receptor isoform distribution might be secondary to the ambient hyperinsulinaemia rather than representing a primary defect.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
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
D007340 Insulinoma A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA. Adenoma, beta-Cell,Insuloma,beta-Cell Tumor,Adenoma, beta Cell,Adenomas, beta-Cell,Insulinomas,Insulomas,Tumor, beta-Cell,Tumors, beta-Cell,beta Cell Tumor,beta-Cell Adenoma,beta-Cell Adenomas,beta-Cell Tumors
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010190 Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA). Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
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
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference

Related Publications

P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
September 1994, The Journal of clinical investigation,
P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
December 1994, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme,
P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
July 1985, Diabetologia,
P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
July 1992, Diabetologia,
P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
May 1992, BMJ (Clinical research ed.),
P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
April 1997, The American journal of physiology,
P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
October 2006, Thrombosis and haemostasis,
P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
September 2001, Nature genetics,
P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
April 2005, Nederlands tijdschrift voor geneeskunde,
P Sbraccia, and M D'Adamo, and F Leonetti, and S Caiola, and P Iozzo, and A Giaccari, and A Buongiorno, and G Tamburrano
December 2010, Regulatory peptides,
Copied contents to your clipboard!