Altered pattern of insulin receptor isotypes in skeletal muscle membranes of type 2 (non-insulin-dependent) diabetic subjects

Diabetologia. 1993 Jul;36(7):628-32. doi: 10.1007/BF00404072.

Abstract

The human insulin receptor exists in two isoforms (HIR-A alpha-subunit 719 amino acids and HIR-B alpha-subunit 731 amino acids) which are generated by alternative splicing of a small exon and display distinct patterns of tissue-specific expression. Using the polymerase chain reaction we have recently shown that skeletal muscle of non-diabetic individuals contains predominantly mRNA encoding HIR-A while in skeletal muscle derived from subjects with Type 2 (non-insulin-dependent) diabetes mellitus similar amounts of each mRNA are expressed. We used a polyclonal antibody which discriminates between HIR-A and HIR-B to assess the isoform expression at the protein level. The antibody showed clearly distinct displacement of insulin binding in skeletal muscle membranes of non-diabetic subjects compared to Type 2 diabetic subjects (displacement of specific 125I-insulin binding: 13 non-diabetic subjects 70.0% +/- 14.34, 12 Type 2 diabetic subjects 32.6% +/- 17.45). A control antibody which does not discriminate between both isoforms showed similar displacement of 125I-insulin in membranes of non-diabetic and Type 2 diabetic subjects. These data suggest that the altered expression of receptor isotype mRNA in the skeletal muscle of Type 2 diabetic subjects leads to an altered receptor isoform pattern in the plasma membrane. While skeletal muscle membranes of non-diabetic subjects contain predominantly HIR-A, membranes of Type 2 diabetic subjects show an increased level of HIR-B in addition to HIR-A.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alternative Splicing
  • Animals
  • Blood Glucose / analysis
  • Cell Line
  • Diabetes Mellitus, Type 2 / metabolism*
  • Glycated Hemoglobin / analysis
  • Humans
  • Insulin / blood
  • Kinetics
  • L-Lactate Dehydrogenase / metabolism
  • Macromolecular Substances
  • Middle Aged
  • Muscles / metabolism*
  • Phosphofructokinase-1 / metabolism
  • Phosphoglucomutase / metabolism
  • Phosphoglycerate Kinase / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Receptor, Insulin / genetics*
  • Receptor, Insulin / metabolism
  • Reference Values
  • Transfection

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Macromolecular Substances
  • RNA, Messenger
  • L-Lactate Dehydrogenase
  • Phosphofructokinase-1
  • Receptor, Insulin
  • Phosphoglycerate Kinase
  • Phosphoglucomutase