Multiple expressions of the activity of guanine nucleotide regulatory protein in human thyroid adenylate cyclase

1982 ◽  
Vol 218 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Sania Amr ◽  
Pierre Carayon ◽  
Michael C. Lin
Keyword(s):  
Adenylate Cyclase ◽  
Regulatory Protein ◽  
Human Thyroid ◽  
Guanine Nucleotide ◽  
Guanine Nucleotide Regulatory Protein

scholarly journals Treatment of streptozotocin-diabetic rats with metformin restores the ability of insulin to inhibit adenylate cyclase activity and demonstrates that insulin does not exert this action through the inhibitory guanine nucleotide regulatory protein Gi

1988 ◽  
Vol 249 (2) ◽  
pp. 537-542 ◽  
Author(s):  
D Gawler ◽  
G Milligan ◽  
M D Houslay
Keyword(s):  
Adenylate Cyclase ◽  
Plasma Membranes ◽  
Regulatory Protein ◽  
Diabetic Rats ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Guanine Nucleotide ◽  
Liver Plasma Membranes ◽  
Streptozotocin Diabetic Rats ◽  
Guanine Nucleotide Regulatory Protein

Insulin caused the inhibition of glucagon-stimulated adenylate cyclase activity in liver plasma membranes, but failed to inhibit this activity in liver membranes from rats made diabetic by treatment with either alloxan or streptozotocin. Treatment of streptozotocin-diabetic rats with insulin, to normalize their blood glucose concentrations, restored this action of insulin. Rats treated with the biguanide drug metformin exhibited a decreased content of the inhibitory guanine nucleotide regulatory protein Gi in liver plasma membranes assessed both structurally, by using a specific polyclonal antibody (AS7), and functionally. Treatment of normal rats with metformin did not alter insulin's ability to inhibit adenylate cyclase in liver plasma membranes; however, metformin treatment of streptozotocin-diabetic rats completely restored this inhibitory action of insulin. Liver plasma membranes from streptozotocin-diabetic animals which either had or had not been treated with metformin had contents of Gi which were less than 10% of those seen in control animals. We conclude that: (i) insulin does not inhibit adenylate cyclase activity through the inhibitory guanine nucleotide regulatory protein Gi; (ii) streptozotocin- and alloxan-induced diabetes elicit a selective insulin-resistant state; and (iii) metformin can exert a post-receptor effect, at the level of the liver plasma membrane, which restores the ability of insulin to inhibit adenylate cyclase.

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