Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetesReport as inadecuate




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Journal of Inflammation

, 9:35

First Online: 01 October 2012Received: 17 June 2012Accepted: 10 September 2012

Abstract

BackgroundObesity is a state of subclinical inflammation resulting in loss of function of insulin receptors and decreased insulin sensitivity. Inhibition of the inflammatory enzymes, matrix metalloproteinases MMPs, for 6 months in rodent models restores insulin receptor function and insulin sensitivity.

MethodsThis 12-week double-blind, randomized, placebo PL-controlled proof-of-concept study was performed to determine if the MMP inhibitor MMPI, doxycycline, decreased global markers of inflammation and enhanced muscle insulin sensitivity in obese people with type 2 diabetes DM2. The study included non-DM2 controls n = 15, and DM2 subjects randomized to PL n = 13 or doxycycline 100 mg twice daily MMPI; n = 11. All participants were evaluated on Day 1; MMPI and PL groups were also evaluated after 84 days of treatment.

ResultsThere was a significant decrease in inflammatory markers C-reactive protein P < 0.05 and myeloperoxidase P = 0.01 in the MMPI but not PL group. The MMPI also significantly increased skeletal muscle activated-total insulin signaling mediators: 3’phosphoinositide kinase-1 PDK1 p < 0.03, protein kinase B PKB-Akt p < 0.004, and glycogen synthase kinase 3ß GSK3ß p < 0.03.

ConclusionsThis study demonstrated short term treatment of people with diabetes with an MMPI resulted in decreased inflammation and improved insulin sensitivity. Larger, longer studies are warranted to determine if doxycycline can improve glucose control in people with diabetes.

Trial RegistrationClinicaltrials.gov NCT01375491

KeywordsDiabetes Doxycycline Insulin sensitivity Matrix metalloproteinases Myeloperoxidase AbbreviationsMMPMatrix metalloproteinase

PLPlacebo

MMPIMMP inhibitor

DM2Type 2 diabetes

PDK13’phosphoinositide kinase-1

PKB-AktProtein kinase B

GSK3 ßGlycogen synthase kinase 3ß

PI3KPhosphatidyl inositol-3-kinase

GLUT4Glucose transporter

CRPC-reactive protein

MPOMyeloperoxidase

OGTTOral glucose tolerance test

DXADual-energy x-ray absorptiometry

A1cHemoglobin A1c

HOMAHomeostasis model assessment.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-9255-9-35 contains supplementary material, which is available to authorized users.

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Author: Karen Frankwich - Courtney Tibble - Moises Torres-Gonzalez - Mariah Bonner - Roy Lefkowitz - Matt Tyndall - Geert W Schmid

Source: https://link.springer.com/







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