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. 2012 Jul-Aug;4(4):302-11.
doi: 10.4161/isl.21374. Epub 2012 Jul 1.

Metabolic syndrome induces changes in KATP-channels and calcium currents in pancreatic β-cells

Myrian Velasco  1 , Carlos Larqué, Gabriela Gutiérrez-Reyes, Reynaldo Arredondo, Carmen Sanchez-Soto, Marcia Hiriart
Affiliations

Metabolic syndrome induces changes in KATP-channels and calcium currents in pancreatic β-cells

Myrian Velasco et al. Islets. 2012 Jul-Aug.

Abstract

Metabolic syndrome (MS) can be defined as a group of signs that increases the risk of developing type 2 diabetes mellitus (DM2). These signs include obesity, hyperinsulinemia and insulin resistance. We are interested in the mechanisms that trigger hyperinsulinemia as a step to understand how β cells fail in DM2. Pancreatic β cells secrete insulin in response to glucose variations in the extracellular medium. When they are chronically over-stimulated, hyperinsulinemia is observed; but then, with time, they become incapable of maintaining normal glucose levels, giving rise to DM2. A chronic high sucrose diet for two months induces MS in adult male Wistar rats. In the present article, we analyzed the effect of the internal environment of rats with MS, on the activity of ATP-sensitive potassium channels (KATP) and calcium currents of pancreatic β cells. After 24 weeks of treatment with 20% sucrose in their drinking water, rats showed central obesity, hyperinsulinemia and insulin resistance, and their systolic blood pressure and triglycerides plasma levels increased. These signs indicate the onset of MS. KATP channels in isolated patches of β cells from MS rats, had an increased sensitivity to ATP with respect to controls. Moreover, the macroscopic calcium currents, show increased variability compared with cells from control individuals. These results demonstrate that regardless of genetic background, a high sucrose diet leads to the development of MS. The observed changes in ionic channels can partially explain the increase in insulin secretion in MS rats. However, some β cells showed smaller calcium currents. These cells may represent a β cell subpopulation as it becomes exhausted by the long-term high sucrose diet.

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Figures

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Figure 1. After 24 weeks of treatment with 20% sucrose in drinking water the MS rats gain weight. Bars represent mean ± SE (n = 91), initial and final weight of control (white bars) and MS group (black bars) *p < 0.01, with respect to final control weight.
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Figure 2. MS rats accumulate peripancreatic and epididymal fat. (A) Bars represent mean ± SE (n = 91) of control (gray bars) and MS rats (black bars), *p < 0.01 with respect to control group. (B) Abdominal circumference, body length and body mass index (BMI). Data are expressed as mean ± SE, (n = 91 rats). **p < 0.01, with respect to control group.
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Figure 3. (A) Control and MS rats, were intraperitoneal (i.p.) injected with glucose (2 g/kg body weight), control in white and MS rats in black symbols. Blood glucose was measured at time shown. Data expressed as mean ± SE **p < 0.05; *p < 0.01 compared with control (n = 27). (B) Insulin (0.2 U/kg body weight) was administered i.p. via to both groups, blood glucose was measured at time shown. Data expressed as mean ± SE, #p < 0.05; compared with control (n = 6).
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Figure 4. Metabolic status after 24 weeks of treatment. (A) Plasma glucose and insulin levels, the bars represent the mean ± SE (n = 61) of control (white bars) and MS rats (black bars) *p < 0.01 with respect to control group. (B) Plasma triglycerides and cholesterol levels (n = 32), systolic blood pressure and cardiac frequency (n = 21). Data are expressed as mean ± SE, **p < 0.01, ***p < 0.05 with respect to control group.
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Figure 5. ATP-sensitive potassium channels in the inside-out patches. (A) KATP channels activity for control patch at different membrane potentials. C, 1 and 2 corresponds to different current levels. (B) Current to voltage relationship for single channels, recorded in inside-out configuration and symmetrical potassium concentration (high potassium solution). The conductance was 53 ± 5 and 50 ± 2 pS for control (n = 9) and MS (n = 13) patches respectively. Data are expressed as mean ± SE.
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Figure 6. Pancreatic β cells from MS rats are more sensitivity to ATP. (A) Effect of ATP over the activity of single potassium channel recorded from control patch (at -50 mV) under control condition, in the presence of ATP (1 mM) and after washout. C, 1 and 2 corresponds to different current levels. (B) Open probability as a function of ATP concentration plot. The data were fitted to Hill equation, Kd and h were: 18.3 ± 0.01 μM and 1 ± 0.01 for control (open circle; n = 6) and 10.1 ± 0.9 μM (p < 0.05 with respect to control), and 0.9 ± 0.01 for MS cell respectively (black circle; n = 13). Data are expressed as mean ± SE.
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Figure 7. Two subpopulations of pancreatic β cells in metabolic syndrome rats according to barium current density. (A) Barium currents families recorded in cells cultured for 24 h, in control (open circle) and two types (MS1 and MS2) pancreatic β cells from MS rats. (B) Current density-voltage relationships of control (open circles, n = 19), MS1 (black circle, n = 13) and MS2 (black square, n = 9). Data are expressed as average ± SE (C) Voltage activation curve for each cell type in (B). The V1/2 and k values are: -0.6 ± 2 mV and 8.4 ± 0.8 for control, and -10 ± 3 mV and 10.3 ± 0.6 for MS1; -5 ± 2 mV and 8.4 ± 0.8 for MS2. Data are expressed as mean ± SE.
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