Cytosolic phosphoenolpyruvate carboxykinase is expressed in α-cells from human and murine pancreas.

The pancreatic islets of Langerhans, mainly formed by glucagon-producing α-cells and insulin-producing ß-cells, are critical for glucose homeostasis. Insulin and glucagon oppositely modulate blood glucose levels in health, but a combined decline in insulin secretion together with increased glucagon secretion contribute to hyperglycemia in diabetes. Despite this bi-hormonal dysregulation, most studies have focused on insulin secretion and much less is known about glucagon secretion. Therefore, a deeper understanding of α-cell metabolism and glucagon secretion is of great interest. Here, we show that phosphoenolpyruvate carboxykinase (PCK1), an essential cataplerotic enzyme involved in metabolism and long considered to be absent from the pancreatic islet, is expressed in pancreatic α-cells of both murine and human. Furthermore, PCK1 transcription is induced by fasting and diabetes in rat pancreas, which indicates that the PCK1 activity is required for α-cell adaptation to different metabolic states. To our knowledge, this is the first evidence implicating PCK1 expression in α-cell metabolism.

Gluconeogenic Enzymes in ß-Cells: Pharmacological Targets for Improving Insulin Secretion.

Pancreatic ß-cells express the gluconeogenic enzymes glucose 6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBP), and phosphoenolpyruvate (PEP) carboxykinase (PCK), which modulate glucose-stimulated insulin secretion (GSIS) through their ability to reverse otherwise irreversible glycolytic steps. Here, we review current knowledge about the expression and regulation of these enzymes in the context of manipulating them to improve insulin secretion in diabetics. Because the regulation of gluconeogenic enzymes in ß-cells is so poorly understood, we propose novel research avenues to study these enzymes as modulators of insulin secretion and ß-cell dysfunction, with especial attention to FBP, which constitutes an attractive target with an inhibitor under clinical evaluation at present.

Sodium tungstate: Is it a safe option for a chronic disease setting, such as diabetes?

Diabetes is a complex metabolic disorder triggered by the deficient secretion of insulin by pancreatic ß cells, the resistance of peripheral tissues to the action of the hormone, or both, and is characterized by chronic hyperglycemia leading to organ damage and failure. Tight glycemic control represents the best therapy to delay or stop progression of diabetes, with many antidiabetic drugs being commercially available nowadays. However, no ideal normoglycemic agent has been developed as yet, and those already available still induce hypoglycemia and/or weight gain as major side effects, worsening glycemic control. In this respect, the inorganic salt sodium tungstate (Na2 WO4 ) has been proven to offer a good antidiabetic alternative in different animal models of diabetes, reducing body weight and normalizing glycemia without causing hypoglycemic episodes. The mechanisms of action mediating the potent antidiabetic actions but also the spectrum of undesirable effects of Na2 WO4 are still poorly understood. In fact, along with its beneficial effects, Na2 WO4 has been consistently reported to be toxic and even carcinogenic. Given that Na2 WO4 is accumulated in the kidneys for elimination, here, we discuss a possible association between long-term Na2 WO4 treatment and a higher risk of renal carcinogenesis in diabetic individuals.

The Antidiabetic Agent Sodium Tungstate Induces Abnormal Glycogen Accumulation in Renal Proximal Tubules from Diabetic IRS2-Knockout Mice.

The kidney is an insulin-sensitive organ involved in glucose homeostasis. One major effect of insulin is to induce glycogen storage in the liver and muscle. However, no significant glycogen stores are detected in normal kidneys, but diabetic subjects present a characteristic renal histopathological feature resulting from extensive glycogen deposition mostly in nonproximal tubules. The mechanism of renal glycogen accumulation is yet poorly understood. Here, we studied in situ glycogen accumulation in the kidney from diabetic IRS2-knockout mice and the effect of the insulin-mimetic agent sodium tungstate (NaW). IRS2-knockout mice displayed hyperglycemia and hyperinsulinemia. NaW only normalized glycemia. There was no evident morphological difference between kidneys from untreated wild-type (WT), NaW-treated WT, and untreated IRS2-knockout mice. However, NaW-treated IRS2-knockout mice showed tubular alterations resembling clear cells in the cortex, but not in the outer medulla, that were correlated with glycogen accumulation. Immunohistochemical detection of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, mostly expressed by renal proximal tubules, showed that altered tubules were of proximal origin. Our preliminary study suggests that IRS2 differentially regulates glycogen accumulation in renal tubules and that NaW treatment in the context of IRS2 ablation induces abnormal glycogen accumulation in cortical proximal tubules.

Asociación entre sedentarismo y malos hábitos alimentarios en estudiantes de nutrición / Association between sedentarism and bad dietary habits among nutrition students

El sedentarismo se relaciona con disminución a la sensibilidad de insulina y acumulación de tejido adiposo visceral. Lo que sumado a malos hábitos alimentarios, explican en parte el aumento global de sobrepeso y obesidad. En Chile el exceso de peso afecta a 64,4% y el sedentarismo al 88,6% de la población.El objetivo es determinar los niveles de sedentarismo en los estudiantes de la carrera de Nutrición y Dietética y evaluar si existe asociación con sus hábitos alimentarios. Se evaluaron 607 estudiantes de la carrera de Nutrición y Dietética aplicándoles una evaluación antropométrica de peso y talla, una encuesta de evaluación alimentaria y una encuesta de actividad física. Resultados: El porcentaje de mujeres sedentarias fue significativamente mayor que en los hombres (74,3% v/s 40,5%). Además,las mujeres que nunca cenabancasi duplicaron el porcentaje observado en los hombres. Finalmente,al comparar 2 grupos de estudiantes, unocompuesto por los que nunca desayunaban, ni cenaban y otro por los que desayunaban y cenaban todos los días,se determinó que existe asociación entre actividad física y la conducta alimentaria (♩2= 10,56; p=0.001) En este estudio se determinó que los individuos jóvenes sedentarios presentaban un mal comportamiento alimentario que quienes realizaban algún tipo de actividad física. Nuestros resultados sugieren que realizar algún tipo de actividad física se asocia a un mejor patrón de alimentación(AU)

A sedentary lifestyle is associated with decreased insulin sensitivity and accumulation of visceral adipose tissue. Which combined with poor eating habits, explain the overall increase in overweight and obesity. In Chile overweight it affects 64.4% and 88.6% sedentary population. The objective was to determine the levels of sedentarism in Nutrition and Dietetics students's and evaluate whether there is an association with eating habits. 607 students from Nutrition and Dietetics were evaluated by applying an anthropometric weight and height assessment, a food assessment survey and a physical activity survey. Results: The percentage of sedentary women was significantly higher than in men (74.3% v / s 40.5%), also women who never eat dinner nearly twice the percentage observed in men. Finally, students who performed some type of physical activity had a significantly higher percentage in the frequency of consumption of breakfast and dinner, with respect to sedentary students. Determining an association between physical activity and eating behaviour (♩2= 10,56; p=0.001). This study determined that young sedentary individuals had a worse eating habits than those who performed some type of physical activity. Our results suggest that perform some type of physical activity is associated with better eating pattern(AU)

Índice de función sexual en mujeres que ejercen el comercio sexual / Sexual function index in women engaged in sex work

ANTECEDENTES: La sexualidad se muestra como un reflejo del nivel de bienestar físico, psicológico y social. Por lo tanto, las experiencias sexuales negativas pueden afectar el completo desarrollo como seres humanos. En Chile no existen estudios que indaguen en la presencia de disfunciones sexuales en la trabajadora sexual. OBJETIVO: El objetivo de este estudio es evaluar el Índice de Función Sexual Femenina (IFSF) en mujeres trabajadoras sexuales con respecto a su desempeño sexual con su pareja estable y compararlas con mujeres no trabajadoras sexuales. MÉTODO: Mujeres sexualmente activas mayores de 18 años. La toma de la muestra fue dirigida no probabilística intencional. El número final a estudiar fue de 58 mujeres, de las cuales 23 mujeres fueron trabajadoras sexuales (grupo estudio) y 35 mujeres que no se dedicaban al comercio sexual (grupo control). RESULTADOS: La edad promedio fue 33 años para el grupo control y de 35 años en el caso de las trabajadoras sexuales. El 4% de las trabajadoras sexuales presentaba estudios universitarios, el 70% se encontraban solteras y utilizaron como principal método anticonceptivo el dispositivo intrauterino. En tanto, el 34% del grupo control presentaba estudios universitarios, el 57% se encontraban solteras y utilizaron como principal método anticonceptivo el hormonal. No hubo diferencias significativas en el IFSF en general y por dominios, entre los grupos. CONCLUSIONES: A pesar de presentar varios factores que aumentan el riesgo de disfunción sexual, las mujeres que desempeñan el comercio sexual no exhiben diferencias significativas en el IFSF respecto al grupo control.

BACKGROUND: Sexuality is displayed as a reflection of the level of physical, psychological and social wellbeing. Therefore, negative sexual experiences can affect the entire development as human beings. In Chile, there are no studies that investigate the presence of sexual dysfunctions in the sex worker. AIM: To evaluate the Female Sexual Function Index (FSFI) in women sex workers about their sexual performance with his regular partner and compared with women not sex workers. METHODS: Sexually active women over 18 years. We work with purposive intentional non probabilistic sampling. The final number of women studied was 58, of which 23 women were sex workers (study group) and 35 women were not involved in the sex trade (control group). RESULTS: The average age was 33 years for the control group and 35 years in the case of sex workers. 4% of sex workers had university education, 70% were unmarried and used as main contraceptive the IUD. Meanwhile, 34% of the control group had university education, 57% were single and used as primary contraceptive the hormone method. There were no significant differences in overall IFSF and domains, between groups. CONCLUSIONS: Despite presenting several factors that increase the risk of sexual dysfunction, women played the sex trade do not exhibit significant differences in the FSFI with respect to the control group.

Over-expression of muscle glycogen synthase in human diabetic nephropathy.

Diabetic nephropathy (DN) is a major complication of diabetic patients and the leading cause of end-stage renal disease. Glomerular dysfunction plays a critical role in DN, but deterioration of renal function also correlates with tubular alterations. Human DN is characterized by glycogen accumulation in tubules. Although this pathological feature has long been recognized, little information exists about the triggering mechanism. In this study, we detected over-expression of muscle glycogen synthase (MGS) in diabetic human kidney. This enhanced expression suggests the participation of MGS in renal metabolic changes associated with diabetes. HK2 human renal cell line exhibited an intrinsic ability to synthesize glycogen, which was enhanced after over-expression of protein targeting to glycogen. A correlation between increased glycogen amount and cell death was observed. Based on a previous transcriptome study on human diabetic kidney disease, significant differences in the expression of genes involved in glycogen metabolism were analyzed. We propose that glucose, but not insulin, is the main modulator of MGS activity in HK2 cells, suggesting that blood glucose control is the best approach to modulate renal glycogen-induced damage during long-term diabetes.

Altered expression and localization of insulin receptor in proximal tubule cells from human and rat diabetic kidney.

Diabetes is the major cause of end stage renal disease, and tubular alterations are now considered to participate in the development and progression of diabetic nephropathy (DN). Here, we report for the first time that expression of the insulin receptor (IR) in human kidney is altered during diabetes. We detected a strong expression in proximal and distal tubules from human renal cortex, and a significant reduction in type 2 diabetic patients. Moreover, isolated proximal tubules from type 1 diabetic rat kidney showed a similar response, supporting its use as an excellent model for in vitro study of human DN. IR protein down-regulation was paralleled in proximal and distal tubules from diabetic rats, but prominent in proximal tubules from diabetic patients. A target of renal insulin signaling, the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK), showed increased expression and activity, and localization in compartments near the apical membrane of proximal tubules, which was correlated with activation of the GSK3ß kinase in this specific renal structure in the diabetic condition. Thus, expression of IR protein in proximal tubules from type 1 and type 2 diabetic kidney indicates that this is a common regulatory mechanism which is altered in DN, triggering enhanced gluconeogenesis regardless the etiology of the disease.

Different involvement for aldolase isoenzymes in kidney glucose metabolism: aldolase B but not aldolase A colocalizes and forms a complex with FBPase.

The expression of aldolase A and B isoenzyme transcripts was confirmed by RT-PCR in rat kidney and their cell distribution was compared with characteristic enzymes of the gluconeogenic and glycolytic metabolic pathway: fructose-1,6-bisphosphatase (FBPase), phosphoenol pyruvate carboxykinase (PEPCK), and pyruvate kinase (PK). We detected aldolase A isoenzyme in the thin limb and collecting ducts of the medulla and in the distal tubules and glomerula of the cortex. The same pattern of distribution was found for PK, but not for aldolase B, PEPCK, and FBPase. In addition, co-localization studies confirmed that aldolase B, FBPase, and PEPCK are expressed in the same proximal cells. This segregated cell distribution of aldolase A and B with key glycolytic and gluconeogenic enzymes, respectively, suggests that these aldolase isoenzymes participate in different metabolic pathways. In order to test if FBPase interacts with aldolase B, FBPase was immobilized on agarose and subjected to binding experiments. The results show that only aldolase B is specifically bound to FBPase and that this interaction was specifically disrupted by 60 microM Fru-1,6-P2. These data indicate the presence of a modulated enzyme-enzyme interaction between FBPase and isoenzyme B. They affirm that in kidney, aldolase B specifically participates, along the gluconeogenic pathway and aldolase A in glycolysis.