Document Detail


β-Cell-specific protein kinase A activation enhances the efficiency of glucose control by increasing acute-phase insulin secretion.
MedLine Citation:
PMID:  23349500     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute insulin secretion determines the efficiency of glucose clearance. Moreover, impaired acute insulin release is characteristic of reduced glucose control in the prediabetic state. Incretin hormones, which increase β-cell cAMP, restore acute-phase insulin secretion and improve glucose control. To determine the physiological role of the cAMP-dependent protein kinase (PKA), a mouse model was developed to increase PKA activity specifically in the pancreatic β-cells. In response to sustained hyperglycemia, PKA activity potentiated both acute and sustained insulin release. In contrast, a glucose bolus enhanced acute-phase insulin secretion alone. Acute-phase insulin secretion was increased 3.5-fold, reducing circulating glucose to 58% of levels in controls. Exendin-4 increased acute-phase insulin release to a similar degree as PKA activation. However, incretins did not augment the effects of PKA on acute-phase insulin secretion, consistent with incretins acting primarily via PKA to potentiate acute-phase insulin secretion. Intracellular calcium signaling was unaffected by PKA activation, suggesting that the effects of PKA on acute-phase insulin secretion are mediated by the phosphorylation of proteins involved in β-cell exocytosis. Thus, β-cell PKA activity transduces the cAMP signal to dramatically increase acute-phase insulin secretion, thereby enhancing the efficiency of insulin to control circulating glucose.
Authors:
Kelly A Kaihara; Lorna M Dickson; David A Jacobson; Natalia Tamarina; Michael W Roe; Louis H Philipson; Barton Wicksteed
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-24
Journal Detail:
Title:  Diabetes     Volume:  62     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-24     Completed Date:  2013-06-28     Revised Date:  2013-07-16    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1527-36     Citation Subset:  AIM; IM    
Affiliation:
Kovler Diabetes Center, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Crosses, Genetic
Cyclic AMP / metabolism*
Cyclic AMP-Dependent Protein Kinases / biosynthesis*,  genetics,  metabolism
Enzyme Induction
Glucose Clamp Technique
Hyperglycemia / metabolism*,  prevention & control
Hypoglycemic Agents / pharmacology,  therapeutic use
Insulin / secretion*
Insulin-Secreting Cells / drug effects,  metabolism*,  secretion
Kinetics
Mice
Mutant Proteins / biosynthesis,  metabolism
Patch-Clamp Techniques
Peptides / pharmacology,  therapeutic use
Phosphorylation / drug effects
Protein Processing, Post-Translational / drug effects
Protein Subunits / biosynthesis,  genetics,  metabolism
Second Messenger Systems* / drug effects
Up-Regulation*
Venoms / pharmacology,  therapeutic use
Grant Support
ID/Acronym/Agency:
DK020595/DK/NIDDK NIH HHS; DK063493/DK/NIDDK NIH HHS; DK074966/DK/NIDDK NIH HHS; DK085129/DK/NIDDK NIH HHS; DK48494/DK/NIDDK NIH HHS; F31 AG035620/AG/NIA NIH HHS; R01 DK085129/DK/NIDDK NIH HHS; T32 DK087703/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Insulin; 0/Mutant Proteins; 0/Peptides; 0/Protein Subunits; 0/Venoms; 141732-76-5/exenatide; 60-92-4/Cyclic AMP; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases
Comments/Corrections
Comment In:
Diabetes. 2013 May;62(5):1389-90   [PMID:  23613561 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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