Expired Study
This study is not currently recruiting Study Participants on ClinicalConnection.com. If you would like to find active studies please search for clinical trials.

Tampa, Florida 33612


The investigators are examining the activation of insulin signaling factors in skeletal muscles of human diabetics. The investigators are characterizing the defects in signaling, and are examining the effects of anti-diabetic agents and exercise on signaling to glucose transport biochemical machinery and whole body glucose disposal.

Study summary:

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.


Inclusion Criteria: - Stable uncomplicated type 2 diabetes - Able to be off oral treatments for 2 months Exclusion Criteria: - Type 1 diabetes - Renal impairment - Cardiovascular disease - Hepatic disease - Insulin therapy needed

Study is Available At:

Original ID:




Secondary ID:

Study Acronym:

Brief Title:

Defective Atypical Protein Kinase C (PKC) Activation in Diabetes and Metabolic Syndrome

Official Title:

Defective Atypical PKC Activation in Diabetes and Metabolic Syndrome

Overall Status:


Study Phase:




Minimum Age:

20 Years

Maximum Age:

80 Years

Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Department of Veterans Affairs

Oversight Authority:

United States: Federal Government

Reasons Why Stopped:

Study Type:


Study Design:

Observational Model: Cohort, Time Perspective: Cro

Number of Arms:


Number of Groups:


Total Enrollment:


Enrollment Type:


Overall Contact Information

Official Name:Robert V Farese, MD
Principal Investigator
Department of Veterans Affairs

Study Dates

Start Date:October 2005
Completion Date:September 2008
Completion Type:Actual
Primary Completion Date:September 2008
Primary Completion Type:Actual
Verification Date:December 2014
Last Changed Date:December 3, 2014
First Received Date:June 2, 2008

Study Outcomes

Outcome Type:Primary Outcome
Measure:Improved insulin signaling with combined metformin-thiazolidinedione treatment.
Time Frame:Insulin signaling in muscle evaluated 6 weeks after combined Met-TZD treatmentall muscle samples ob
Safety Issues:False

Study Interventions

There are no available Study Interventions

Study Arms

Study Arm Type:Other
Arm Name:Group 1

Study Agencies

Agency Class:U.S. Fed
Agency Type:Lead Sponsor
Agency Name:Department of Veterans Affairs

Samples and Retentions

Sample Retention:None Retained
Description: Muscle biopsies taken before and after insulin stimulation in euglycemic clamp studies
Study Population: type 2 diabetes controlled by diet or oral agents and comparable non-diabetic control subjects
Sample Method:Non-Probability Sample

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.

This study is not currently recruiting Study Participants. The form below is not enabled.