Metabolic processes
Insulin sensitising action of chromium picolinate in various experimental models of diabetes mellitus

https://doi.org/10.1016/j.jtemb.2004.03.002Get rights and content

Abstract

Although chromium is an essential element for carbohydrate and lipid metabolism, its effects in diabetic patients are still debated. We have studied the effect of 6 week treatment with chromium picolinate (8 μg/ml in drinking water) in streptozotocin (STZ)-induced type 1 and type 2 diabetic rat models. The mechanism of anti-diabetic action of chromium picolinate was studied using C2C12 myoblasts and 3T3-L1 adipocytes. Chromium picolinate significantly decreased the area under the curve over 120 min for glucose of both STZ-induced type 1 (40 mg/kg, i.v. in adult rats) and type 2 (90 mg/kg, i.p. in 2 day old rat neonates) diabetic rats without any significant change in area under the curve over 120 min for insulin as compared to controls. The composite insulin sensitivity index and insulin sensitivity index (KITT) values of both type 1 and type 2 diabetic rats were increased significantly by chromium picolinate. Treatment with chromium picolinate produced a significant decrease in elevated cholesterol and triglyceride levels in both types of diabetic rats. In 3T3-L1 adipocytes, chromium picolinate (0–10 μmol) per se did not produce any effect, however, when co-incubated with insulin it significantly increased the intracellular triglyceride synthesis (EC50=363.7 nmol/l). Similarly in C2C12 myoblasts, chromium picolinate alone did not produce any effect, however, it significantly increased insulin-induced transport of 14C-glucose. In conclusion, chromium picolinate significantly improves deranged carbohydrate and lipid metabolism of experimental chemically induced diabetes in rats. The mechanism of in vivo anti-diabetic action appears to be peripheral (skeletal muscle and adipose tissue) insulin enhancing action of chromium.

Introduction

Insulin resistance has emerged as an important pathophysiological abnormality in diabetes mellitus. Presence of insulin resistance in both type 1 and type 2 diabetes mellitus has been observed both clinically [1], [2], [3] as well as experimentally [4], [5], [6]. Absolute (as in case of type 1 diabetes mellitus) or relative (as in case of type 2 diabetes mellitus) lack of insulin is thought to render the target organs resistant to actions of insulin. Resistance to insulin action in skeletal muscle, adipose tissue and liver contributes to hyperglycemia as well as plays an important role in the pathogenesis of long-term complications [7]. Therefore, treatments that improve peripheral insulin resistance would be beneficial in the long-term management of these patients.

Chromium, a group VIb transition element, is an essential element required for normal carbohydrate and lipid metabolism [8]. Deficiency of chromium has been found to cause glucose intolerance which is an indicator of insulin resistance in humans [9], [10] as well as experimental animals [11], [12]. Studies in animals reported that chromium supplementation resulted in at least partial reversal of glucose tolerance [13], [14], [15]. However, when these studies were done in man, variable results were obtained. While various well-controlled clinical trials showed improvement in glucose tolerance [16], [17], [18], others found improvement only in 40–60% of the patients evaluated [19], [20], [21]. In some well-controlled clinical trials chromium failed to produce any response [22], [23], [24], [25] but one of the studies rather reported deterioration of glucose control [26]. It has also been observed that subjects with good glucose tolerance who do not need additional chromium do not respond to supplemental chromium [9], [27]. Subjects consuming adequate chromium and well balanced diets also do not respond to additional chromium [22]. Moreover, most of the investigators reporting beneficial effects with chromium supplementation in clinical [17], [28], [29] as well as experimental [30], [31], [32] set-up found that observed effects of chromium depended upon the existence of a deficiency state. Hence, it is claimed that chromium is a nutrient and not a drug and will therefore benefit only those who are deficient or marginally deficient in chromium [10]. Thus, although the essentiality of chromium in normal glucose homeostasis has been established, its usefulness as a therapeutic agent for the treatment of diabetes mellitus of variable etiology (other than chromium deficiency) remains questionable. Hence, the objective of the present investigation was to study the effect of chromium picolinate on insulin resistance in experimental models of diabetes mellitus.

Section snippets

Animals

Wistar rats from an inbred colony were bred under well-controlled conditions of temperature (22±2°C), humidity (55±5%) and a 12/12 h light-dark cycle with 07h30–19h30 being light phase. Conventional laboratory diet and tap water were provided ad libitum. The protocol of the experiment was approved by the Institutional Animal Ethical Committee as per the guidance of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Social Justice and

General characteristics

The general characteristics of the experimental animals at the end of 6 weeks of treatment schedule are summarised in Table 1, Table 2. Type 1 diabetic control animals exhibited significantly lower body weights as compared to their non-diabetic counterparts (Table 1). However, body weights of type 2 diabetic control rats were not significantly different from that of non-diabetic control rats (Table 2). Chronic treatment with chromium picolinate did not produce any significant effect on body

Discussion

Chromium is reported to be an essential element required for normal carbohydrate and lipid metabolism [10]. Lack of dietary chromium has been reported to lead to the development of abnormal glucose tolerance in rats [1], [4], [13], [38]. Moreover, it is reported that the impairment of glucose tolerance was the earliest recognised symptom of a low chromium state in animals [19]. However, in the present investigation corresponding non-diabetic control rats of both type 1 and type 2 diabetic rats

Acknowledgements

We wish to acknowledge the Senior Research Fellowship awarded to Ms Urmila A. Shinde by the Council of Scientific and Industrial Research, New Delhi (No. 8/261(1)/99-EMR-I-(SPS)). The work was also supported by a research grant from All India Council of Technical Education, New Delhi. Chromium picolinate was a generous gift by Softcaps Pvt. Ltd., Chennai, India.

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