Monosodium glutamate (MSG)-obese rats develop glucose intolerance and insulin resistance to peripheral glucose uptake

Abstract

Different levels of insulin sensitivity have been described in several animal models of obesity as well as in humans. Monosodium glutamate (MSG)-obese mice were considered not to be insulin resistant from data obtained in oral glucose tolerance tests. To reevaluate insulin resistance by the intravenous glucose tolerance test (IVGTT) and by the clamp technique, newborn male Wistar rats (N = 20) were injected 5 times, every other day, with 4 g/kg MSG (N = 10) or saline (control; N = 10) during the first 10 days of age. At 3 months, the IVGTT was performed by injecting glucose (0.75 g/kg) through the jugular vein into freely moving rats. During euglycemic clamping plasma insulin levels were increased by infusing 3 mU . kg -1 . min -1 of regular insulin until a steady-state plateau was achieved. The basal blood glucose concentration did not differ between the two experimental groups. After the glucose load, increased values of glycemia (P<0.001) in MSG-obese rats occurred at minute 4 and from minute 16 to minute 32. These results indicate impaired glucose tolerance. Basal plasma insulin levels were 39.9 ± 4 µU/ml in control and 66.4 ± 5.3 µU/ml in MSG-obese rats. The mean post-glucose area increase of insulin was 111% higher in MSG-obese than in control rats. When insulinemia was clamped at 102 or 133 µU/ml in control and MSG rats, respectively, the corresponding glucose infusion rate necessary to maintain euglycemia was 17.3 ± 0.8 mg . kg -1 . min -1 for control rats while 2.1 ± 0.3 mg . kg -1 . min -1 was sufficient for MSG-obese rats. The 2-h integrated area for total glucose metabolized, in mg . min . dl -1 , was 13.7 ± 2.3 vs 3.3 ± 0.5 for control and MSG rats, respectively. These data demonstrate that MSG-obese rats develop insulin resistance to peripheral glucose uptake.

Decreased lipolysis and enhanced glycerol and glucose utilization by adipose tissue prior to development of obesity in monosodium glutamate (MSG) treated-rats

“…The decreased HSL activity and mRNA expression, found in adipose tissue of our MSG-treated rats also supports this conclusion, since conditions of hyperinsulinemia and decreased insulin sensitivity, like that taking place during late pregnancy, are known to have the opposite effect on these variables. 21 Enhanced insulin sensitivity in 1 month old MSG-rats may occur despite hyperinsulinemia and insulin resistance being reported in adult MSG-rats, 51 since a similar transient insulin hypersensitivity followed by decreased insulin responsiveness in white adipose tissue has been reported to occur in both VMH-induced obesity 52 and obese Zucker rats. 53 The present ®ndings do not allow us to establish the order of the different factors contributing to the later development of obesity in the MSG rats.…”

Atorvastatin improves insulin sensitivity in mice with obesity induced by monosodium glutamate

“…And there are no reports exist of their mechanism of action in insulin resistance, obesity animal models. We investigated the effect of atorvastatin on glucose metabolism and insulin resistance and the mechanism of action in MSG-induced obese mice, a model of T2DM with obesity, hyperinsulinemia, insulin resistance, hyperlipidemia and hyperglycemia [24] . Atorvastatin significantly inhibited the plasma glucose and decreased the plasma insulin level and the HOMA-IR index but increased the ISI in obese mice.…”

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

“…Neonate male Wistar rats were subcutaneously injected during the first 5 days of life with MSG at a dose of 4 g/kg of body weight (BW) (Olney 1969, Hirata et al 1997. Control animals received equimolar saline solution.…”

“…Regarding this matter, subdiaphragmatic vagotomy (VAG) has been performed to attenuate the hyperinsulinemia in monosodium l-glutamate (MSG)-treated rats and other obese models such as Wistar fatty models (Yamatani et al 1998, Balbo et al 2000. The MSG rat is an interesting model that reconciles increased parasympathetic activity, hyperinsulinemia, and obesity, among other components of the metabolic syndrome, mimicking the disorders observed in obese individuals (Hirata et al 1997, Dolnikoff et al 2001, Karlen-Amarante et al 2012.…”