[Adenylyl cyclase signaling mechanisms of the insulin superfamily peptide action and their impairment in myometrium of pregnant women with type 2 diabetes].
For the first time we found in myometrium of the women and pregnant women that adenylyl cyclase (AC) stimulating effects of relaxin, insulin and insulin growth factor 1 are realized via six-component AC signaling mechanisms involving the following signaling chain: receptor-tyrosine kinase ==> Gi protein (beta gamma dimmer) ==> phosphatidylinositol 3-kinase ==> protein kinase C (zeta) ==> Gs protein ==> adenylyl cyclase (AC), which are similar to the discovered adenylyl cyclase signaling mechanisms of insulin and relaxin action in vertebrates (rat) and invertebrates (mollusk). The effect of relaxin is more pronounced as compared with other peptides (relaxin > insulin > insulin-like growth factor-1) in myometrium of pregnant women. It is connected with the specific role ofrelaxin as main regulator of reproductive functions. For the first time we revealed the functional defects in distal parts of adenylyl cyclase signaling mechanisms of the insulin superfamily peptides action in the condition type-2 diabetes (the increase of the basal adenylyl cyclase activity and decrease of the peptide-stimulated AX activity in presence of guanilylimidodiphosphate). The defects are localized on the level of Gs protein, adenylyl cyclase and their functional coupling. The data obtained confirm our conception about molecular defects in hormoneregulated adenylyl cyclase system as a key reason of type-2 diabetes.
Plesneva
S a
Sa
Kuznetsova
L A
LA
Shpakov
A O
AO
Sharova
T S
TS
Pertseva
M N
MN
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009215:Myometrium / Q000201:enzymology*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D012065:Relaxin / Q000378:metabolism*; D015398:Signal Transduction
D007328:Insulin; D009124:Muscle Proteins; D007334:Insulin-Like Growth Factor I; D012065:Relaxin; D000262:Adenylyl Cyclases