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Publication
ß-Cell-specific protein kinase A activation enhances the efficiency of glucose
control by increasing acute-phase insulin secretion.
Authors Kaihara KA, Dickson LM, Jacobson DA, Tamarina N, Roe MW, Philipson LH, Wicksteed
B
Submitted By Submitted Externally on 7/24/2018
Status Published
Journal Diabetes
Year 2013
Date Published 5/1/2013
Volume : Pages 62 : 1527 - 36
PubMed Reference 23349500
Abstract 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 ß-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 ß-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 ß-cell exocytosis.
Thus, ß-cell PKA activity transduces the cAMP signal to dramatically increase
acute-phase insulin secretion, thereby enhancing the efficiency of insulin to
control circulating glucose.




Strains




Genes
SymbolDescription
Prkacaprotein kinase, cAMP dependent, catalytic, alpha

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