Calpain Activity in Leukocytes Is Associated with Diabetes Biochemical Markers.

BACKGROUND AND AIMS: CAPN10 gene is associated with type 2 diabetes (T2D). Specific members of the calpain system (CAPN1, CAPN2 and CAPN10) are implicated in glucose metabolism. The aim of this study was to evaluate the calpain activity in leukocytes of control subjects and patients with T2D and its association with the calpain family members involved in glucose metabolism and with biochemical parameters that are altered in T2D. METHODS: Calpain activity under extracellular glucose concentrations (70-280 mg/dL) was evaluated in leukocytes from subjects with and without T2D. Protein and mRNA levels of CAPN1, CAPN2 and CAPN10 were evaluated. Calpain inhibitors assays were performed in leukocytes from subjects without T2D to evaluate glucose uptake. Calpain activity at 100 mg/dL glucose was correlated with biochemical parameters by multivariate regression. RESULTS: Calpain activity in control subjects increased with extracellular glucose concentration in a dose-dependent manner, showing a negative association with HbA1c levels and total amount of CAPN10 protein. In contrast, calpain activity is decreased in patients with T2D and do not respond to changes in glucose concentration. A reduction of CAPN1 autolytic fragments were observed in the subjects with diabetes. Calpain inhibitors decreased calpain activity but did not altered glucose uptake in leukocytes. CONCLUSIONS: Calpain activity induced by glucose in leukocytes was associated with biochemical markers of glucose metabolism and with CAPN10 protein abundance. Calpain activity is low in subjects with T2D. Thus, calpain activity induced by extracellular glucose in leukocytes could be a potential marker for T2D early risk detection.

Genetic determinants for gestational diabetes mellitus and related metabolic traits in Mexican women.

Epidemiological and physiological similarities among Gestational Diabetes Mellitus (GDM) and Type 2 Diabetes (T2D) suggest that both diseases, share a common genetic background. T2D risk variants have been associated to GDM susceptibility. However, the genetic architecture of GDM is not yet completely understood. We analyzed 176 SNPs for 115 loci previously associated to T2D, GDM and body mass index (BMI), as well as a set of 118 Ancestry Informative Markers (AIMs), in 750 pregnant Mexican women. Association with GDM was found for two of the most frequently replicated T2D loci: a TCF7L2 haplotype (CTTC: rs7901695, rs4506565, rs7903146, rs12243326; P=2.16 x 10(-06); OR=2.95) and a KCNQ1 haplotype (TTT: rs2237892, rs163184, rs2237897; P=1.98 x 10(-05); OR=0.55). In addition, we found two loci associated to glycemic traits: CENTD2 (60' OGTT glycemia: rs1552224, P=0.03727) and MTNR1B (HOMA B: rs1387153, P=0.05358). Remarkably, a major susceptibility SLC16A11 locus for T2D in Mexicans was not shown to play a role in GDM risk. The fact that two of the main T2D associated loci also contribute to the risk of developing GDM in Mexicans, confirm that both diseases share a common genetic background. However, lack of association with a Native American contribution T2D risk haplotype, SLC16A11, suggests that other genetic mechanisms may be in play for GDM.

[Obesity and metabolic syndrome. A challenge for the Mexican Institutes of Health]. / La obesidad y el síndrome metabólico. Un reto para los Institutos Nacionales de Saluda.

Numerous efforts for the development of basic and clinical research in obesity are being made by the National Institutes of Health and Federal Reference Hospitals in Mexico. However, greater interaction among researchers and stronger efforts towards the dissemination of the results are needed. The document outlines the general ideas and proposals of the Academic Group for the Study, Prevention and Treatment of Obesity and Metabolic Syndrome of the Coordinating Committee of the National Institutes of Health and High Specialty Hospitals (CCINSHAE). This is the first step in developing common objectives, with the aim of understanding the effect of these entities in public health and to establish guidelines to limit and eventually overcome them. We discuss the appropriateness of analyzing obesity and the metabolic syndrome together, and the current management of these entities at the National Institutes of Health in Mexico. The problems that arise in clinical practice lead to the need to generate a new model of medical care, including a new health worker and a new patient. It is imperative to establish permanent lines of communication and education with health personnel and with patients. The group proposes an integrated approach for research in these areas. Finally, a master plan that links the National Institutes of Health, particularly in the areas of research and programs within the institutions, is required as a first step in seeking answers useful in solving the problem. The second step would be linking the first and second levels of care through concrete actions needed to limit and reduce obesity and metabolic syndrome in the population.

The activity of calpains in lymphocytes is glucose-dependent and is decreased in diabetic patients.

Calpains are nonlysosomal calcium-dependent cysteine proteases that participate in insulin secretion and action. Polymorphisms in the calpain-10 gene have been shown to increase the risk for type 2 diabetes. Since white blood cells have been used to study glucose homeostasis, the present study was carried to find out if calpains have different activity and/or expression in accessible cells such as lymphocytes of individuals with or without type 2 diabetes. Fasting blood glucose concentration was significantly higher in diabetic subjects, whereas the difference in the activity of calpains evaluated in basal and stimulating extracellular glucose concentration was significantly higher in the lymphocytes from the control group. The mRNA expression of calpain-10 was similar in the lymphocytes of both patients and controls. The protein blots showed four bands that ranged between 75 and 50 kDa; however, no statistical differences were observed in the expression of the calpain-10 isoforms between controls and patients. Data obtained showed that human lymphocytes express calpain-10 mRNA and protein, showing a similar expression between diabetic and control subjects, nevertheless in the diabetic group calpain activity was less glucose-sensitive.

Hiperhomocisteinemia: un nuevo factor de riesgo coronario / Hyperhomocysteinemia: a new factor in coronary risk

Las enfermedades cardiovasculares son la principal causa de mortalidad tanto en México como en otros países occidentales. Los factores de riesgo ateroscleróticos convencionales tales como: el tabaquismo, la hipertensión arterial sistémica, diabetes mellitus e hipercolesterolemia no explican totalmente esta asociación. Recientemente se ha reconocido que la hiperhomocisteinemia contribuye al proceso aterosclerótico de manera directa o en asociación a estos factores de riesgo al promover una lesión endotelial e inducir estrés oxidativo en la pared vascular. La homocisteína es un aminoácido generado en condiciones fisiológicas tras la ingesta de alimentos protéicos, utilizada en diversas vías metabólicas. Niveles elevados de este amino ácido en plasma (mayores de 15 mmol/L o menores en presencia de otros factores de riesgo coronario), promueven el desarrollo de aterosclerosis. El uso de suplementos de ácido fólico, vitamina B6 y B12 disminuyen de manera efectiva los niveles de homocisteína en plasma, por lo que es posible que tengan un papel importante en la prevención y manejo de la enfermedad vascular aterosclerótica.

Dos casos de feminización testicular / Two cases of testicular feminization

Se presentan los casos de dos hermanos con síndrome de resistencia a los andrógenos en su variante de feminización testicular. Las edades al momento del diagnóstico fueron 14 y 17 años respectivamente; el más joven de los dos acudió a consulta por una tumoración en la región inguinal que resultó ser un testículo; el hermano fue estudiado porque al realizar su historia clínica se encontró que tenía amenorrea. Se describen los hallazgos físicos, los estudios psicológico y genético, y se explica el tratamiento que se les dio.