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Tissue kallikrein deficiency, insulin resistance, and diabetes in mouse and man.

Abstract : The kallikrein-kinin system has been suggested to participate in the control of glucose metabolism. Its role and the role of angiotensin-I-converting enzyme, a major kinin-inactivating enzyme, are however the subject of debate. We have evaluated the consequence of deficiency in tissue kallikrein (TK), the main kinin-forming enzyme, on the development of insulin resistance and diabetes in mice and man. Mice with inactivation of the TK gene were fed a high-fat diet (HFD) for 3 months, or crossed with obese, leptin-deficient (ob/ob) mice to generate double ob/ob-TK-deficient mutants. In man, a loss-of-function polymorphism of the TK gene (R53H) was studied in a large general population cohort tested for insulin resistance, the DESIR study (4843 participants, 9 year follow-up). Mice deficient in TK gained less weight on the HFD than their WT littermates. Fasting glucose level was increased and responses to glucose (GTT) and insulin (ITT) tolerance tests were altered at 10 and 16 weeks on the HFD compared with standard on the diet, but TK deficiency had no influence on these parameters. Likewise, ob-TK⁻/⁻ mice had similar GTT and ITT responses to those of ob-TK⁺/⁺ mice. TK deficiency had no effect on blood pressure in either model. In humans, changes over time in BMI, fasting plasma glucose, insulinemia, and blood pressure were not influenced by the defective 53H-coding TK allele. The incidence of diabetes was not influenced by this allele. These data do not support a role for the TK-kinin system, protective or deleterious, in the development of insulin resistance and diabetes.
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Contributor : Laurent Jonchère <>
Submitted on : Tuesday, March 24, 2015 - 11:37:07 AM
Last modification on : Thursday, January 14, 2021 - 11:29:09 AM

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Louis Potier, Ludovic Waeckel, Fréderic Fumeron, Sophie Bodin, Marinos Fysekidis, et al.. Tissue kallikrein deficiency, insulin resistance, and diabetes in mouse and man.. Journal of Endocrinology, BioScientifica, 2014, 221 (2), pp.297-308. ⟨10.1530/JOE-13-0529⟩. ⟨hal-01134775⟩



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