Intramyocellular Fatty Acid Trafficking in Insulin Resistance States - Effects of Intestinal Delivery of Lipids

Overview

About this study

Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking is responsible for muscle insulin resistance, although it has been shown that raising FFA with Intralipid can cause muscle insulin resistance within 4 hours. We do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. We propose to alter the profile and concentrations of FFA of healthy, non-obese adults using an overnight, intra-duodenal palm oil infusion vs. an intra-duodenal Intralipid infusion (both compared to saline control). We will compare the muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates, providing the first measure of how different FFA profiles alter muscle FFA trafficking and insulin action at the whole body and cellular/molecular levels. By identifying which steps in the insulin signaling pathway are most affected, we will determine the site-specific effect of ceramides and/or DG on different degrees of insulin resistance.
Hypothesis 1: Palm oil infusion will result in abnormal FFA trafficking into intra-myocellular ceramides and abnormal insulin signaling.
Hypothesis 2: Intralipid infusion will result in abnormal FFA trafficking into intra-myocellular saturated DG and abnormal insulin signaling.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria: 

  • Premenopausal women and men.
  • BMI 18-27.
  • Weight stable.
  • Not pregnant/nursing

Exclusion Criteria:

  • Ischemic heart disease.
  • - Atherosclerotic valvular disease.
  • Smokers (> 20 cigarettes per week).
  • Bilateral oophorectomy.
  • Concomitant use of medications that can alter serum lipid profile (high dose fish oil, statins, niacin, fibrates, thiazolinediones, beta-blockers, atypical antipsychotics).
  • Lidocaine allergy.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Michael Jensen, M.D.

Open for enrollment

Contact information:

Pamela Reich

(507)255-6062

Reich.Pamela@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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CLS-20478968

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