Defective Atypical Protein Kinase C (PKC) Activation in Diabetes and Metabolic Syndrome
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|ClinicalTrials.gov Identifier: NCT00690755|
Recruitment Status : Completed
First Posted : June 5, 2008
Results First Posted : May 19, 2016
Last Update Posted : May 19, 2016
|Condition or disease|
|Diabetes Mellitus, Type 2|
We have provided clear evidence that insulin activation of all three signaling components, Viz., IRS-1-dependent PI 3-Kinase, atypical protein kinase C (aPKC) and PKB/Akt is defective in diabetic muscle. These defects are best seen when insulin activation is conducted at both half-maximal and maximal stimulation. Moreover, whereas previous studies had shown that treatment with metformin (Met) alone improves aPKC activation, or that treatment with thiazolidinedione (TZD) alone produces increases in activation of IRS-1/PI3K and aPKC when evaluated at maximal insulin stimulation, we have recently found that combined treatment with Met plus TZD for 6 weeks provokes marked increases in insulin effects on all three signaling factors at both half-maximal and maximal insulin stimulation. This work is being prepared for submission for publication.
We have also evaluated the improvement in insulin signaling in diabetic muscle 4 hours after acute endurance (one-legged) exercise and found that the responsiveness of aPKC to the lipid PI3K-derived activator, PIP3, was improved. Also increased was the activation by insulin of IRS-2-dependent PI3K, ERK1/2, and downstream protein synthesis machinery, viz., p70S6 kinase and eukaryotic elongation factor eEF2. These effects of exercise would be expected to enhance glucose transport and utilization by muscle, and promote protein synthesis, i.e., an anabolic response.
|Study Type :||Observational|
|Actual Enrollment :||157 participants|
|Official Title:||Defective Atypical PKC Activation in Diabetes and Metabolic Syndrome|
|Study Start Date :||May 2000|
|Actual Primary Completion Date :||September 2012|
|Actual Study Completion Date :||September 2012|
type 2 diabetic individuals
type 1 diabetic individuals or those with diabetes secondary to pancreatic disease
non-diabetic individuals who are not considered to be overweight
non-diabetic individuals who are considered to be overweight
non-diabetic and type 2 diabetic individuals who will be subjected to an exercise study
individuals who have or are suspected of having glucose intolerance, including patients who have a history of gestational diabetes and patients who have polycystic ovary syndrome
healthy non-diabetic subjects who will receive one dose of metformin orally 1-2 hours before performing procedures
- Alterations in PKC-zeta mRNA in Vastus Lateralis Skeletal Muscles [ Time Frame: PKC-zeta mRNA levels and aPKC activity in muscle evaluated 40 minutes post-insulin treatment ]All muscle samples obtained by 9/30/07, final date for examination of samples 9/30/08 Muscle dependent ability to diminish blood glucose levels during insulin treatment.
Biospecimen Retention: None Retained
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00690755
|United States, Florida|
|VA Medical Center|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Robert V Farese, MD||VA Office of Research and Development|