Hiriart-Urdanivia M, Sánchez-Soto C, Velasco M, Sabido-Barrera J, Ortiz-Huidobro RI

Language: Spanish
References: 7
Page: 541-545
PDF size: 179.06 Kb.

ABSTRACT

The metabolic syndrome describes a group of signs that increase the likelihood for developing type 2 diabetes mellitus, cardiovascular diseases and some types of cancer. The action of insulin depends on its binding to membrane receptors on its target cells. We wonder if blood insulin could travel bound to proteins and if, in the presence of hyperinsulinemia, a soluble insulin receptor might be generated. We used young adult Wistar rats (which have no predisposition to obesity or diabetes), whose drinking water was added 20 % of sugar and that were fed a standard diet ad libitum for two and six months. They were compared with control rats under the same conditions, but that had running water for consumption. At two months, the rats developed central obesity, moderate hypertension, high triglyceride levels, hyperinsulinemia, glucose intolerance and insulin resistance, i.e. metabolic syndrome. Electrophoresis of the rats’ plasma proteins was performed, followed by Western Blot (WB) for insulin and for the outer portion of the insulin receptor. The bands corresponding to insulin and to the receptor external part were at the same molecular weight level, 25-fold higher than that of free insulin. We demonstrated that insulin, both in control animals and in those with hyperinsulinemia, travels bound to the receptor outer portion (ectodomain), which we called soluble insulin receptor, and that is released al higher amounts in response to plasma insulin increase; in rats with metabolic syndrome and hyperinsulinemia, plasma levels are much higher than in controls. Soluble insulin receptor increase in blood might be an early sign of metabolic syndrome.

REFERENCES

1. Hiriart M, Velasco M, Larqué C, Díaz-García CM. Metabolic syndrome and ionic channels in pancreatic beta cells. Vitam Horm. 2014;95:87-114.

2. Velasco M, Larqué C, Gutiérrez-Reyes G, Arredondo R, Sánchez-Soto C, Hiriart M. Metabolic syndrome induces changes in KATP-channels and calcium currents in pancreatic β-cells. Islets. 2012;4:302-311.

3. Hiriart M, Sánchez-Soto C, Díaz-García CM, Castanares DT, Avitia M, Velasco M, et al. Hyperinsulinemia is associated with increased soluble insulin receptors release from hepatocytes. Front Endocrinol (Lausanne). 2014;5:95.

4. Tatulian SA. Structural dynamics of insulin receptor and transmembrane signaling. Biochemistry. 2015;54:5523-5532.

5. Larque C, Velasco M, Navarro-Tableros V, Duhne M, Aguirre J, Gutiérrez- Reyes G, et al. Early endocrine and molecular changes in metabolic syndrome models. IUBMB Life. 2011;63:831-839.

6. Soluble Insulin Receptor Study Group. Soluble insulin receptor ectodomain is elevated in the plasma of patients with diabetes. Diabetes. 2007;56:2028-2035.

7. Yuasa T, Amo K, Ishikura S, Nagaya H, Uchiyama K, Hashida S, et al. Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells. Biochem Biophys Res Commun. 2014;445:236-243.