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Joslin researchers gain new understanding of diabetes and kidney disease
Date:7/23/2012

ant in the intestine, are also found in the endothelium and kidney.

The Joslin study investigated the effects of GLP-1 in non-diabetic and diabetic mice with an "overexpression" of the enzyme PKCβ (protein kinase C-beta) which is produced in excess when blood glucose is high. Excess PKCβ can lead to diabetes complications, including kidney disease. PKCβ enhances the action of angiotensin II (Ang II), a peptide hormone that affects renal filtration and blood flow and also regulates blood pressure, which increases inflammation and accelerates the progression of kidney damage.

The study looked at the interactions of GLP-1, PKC-beta and ANG II that affect GLP-1's protective action in renal endothelial cells. "We've been interested in diabetic kidney disease for a long time, particularly the role of PKCβ and Ang II in promoting kidney damage," says Dr. King. "We were interested in investigating how GLP-1 could protect against the effects of hyperglycemia on renal function."

Josin researchers made two major findings: They identified the mechanisms by which GLP-1 can induce protective actions on the glomerular (renal) endothelial cells by inhibiting the signaling pathway of Ang II and its pro-inflammatory effect; and demonstrated a dual signaling mechanism by which hyperglycemia, via PKCβ activation, can increase Ang II action and inhibit GLP-1's protective effects by reducing the expression of GLP-1 receptors in the glomerular endothelial cells. "We know that people with diabetes are more sensitive to Ang II; our data suggests one reason why," says Dr. King.

The results suggest that effective therapeutic agents could be developed to enhance the effects of GLP-1R on the endothelium which may prevent glomerular endothelial dysfunction and slow the progression of diabetic nephropathy. "We now know that increased PKCβ decreases GLP-1R which makes the kidney less responsive to treatment with GLP-1-based drugs
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Contact: Jeffrey Bright
jeffrey.bright@joslin.harvard.edu
617-309-1957
Joslin Diabetes Center
Source:Eurekalert  

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