Altered pattern of insulin receptor isotypes in skeletal muscle membranes of type 2 (non-insulin-dependent) diabetic subjects.
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.
Kellerer
M
M
Institut für Diabetesforschung, Munich, Germany.
Sesti
G
G
Seffer
E
E
Obermaier-Kusser
B
B
Pongratz
D E
DE
Mosthaf
L
L
Häring
H U
HU
D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D046911:Macromolecular Substances; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D010732:Phosphofructokinase-1 / Q000378:metabolism; D010733:Phosphoglucomutase / Q000378:metabolism; D010735:Phosphoglycerate Kinase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D014162:Transfection
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D007770:L-Lactate Dehydrogenase; D046911:Macromolecular Substances; D010732:Phosphofructokinase-1; D010733:Phosphoglucomutase; D010735:Phosphoglycerate Kinase; D012333:RNA, Messenger; D011972:Receptor, Insulin