The SA Journal Diabetes & Vascular Disease Vol 14 No 2 (December 2017)

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RESEARCH ARTICLE SA JOURNAL OF DIABETES & VASCULAR DISEASE
72 VOLUME 14 NUMBER 2 • DECEMBER 2017
Impairment of insulin-stimulated glucose transport is considered
themost consistent change that develops early in the hearts of animal
models of insulin resistance.26 Since GLUT4 is the most prominent
glucose transporter in differentiated cardiomyocytes,49 our data
underscore the importance of further investigation analysing the
expression of intermediates of insulin signal transduction and
the effects of melatonin treatment thereupon in cardiomyocytes
isolated from treated control and obese hearts.
The effect of six weeks of melatonin treatment on the basal
expression and activation of a number of intermediates inmyocardial
tissue from control and obese rats has been studied previously in
our laboratory: baseline activation of PKB/ Akt, extracellular signal-
regulated kinase (ERK) p42/p44 and glycogen synthase kinase 3 beta
(GSK3β) were found to be significantly upregulated by melatonin
treatment in both control and obese rats.33 However, it will be also
important to determine whether these observed beneficial changes
were secondary to the improved whole-body insulin sensitivity or
whether there were changes in cardiomyocyte protein expression
and activation per se elicited by melatonin treatment.
In this regard, a marginal increase in GLUT4 expression was
previously reported to be associated with an increase in glucose
uptake by melatonin-treated adipose tissue.41 Our additional
observations showed significant increases in GLUT4 expression
in the whole heart tissue of obese rats after six weeks of in vivo
melatonin treatment (Fig. 6). Interestingly, as expected, the
significant lowering in glucose uptake by cardiomyocytes from
obese rats was also reflected in the reduction in PKB/Akt activation
when compared with their age-matched controls (Fig. 7).
Conclusion
To our knowledge, this is the first study on the role of melatonin in
cardiacglucoseuptake inan insulin-resistant state. Thecardiovascular
benefits of melatonin supplementation are supported by the fact
that circulating melatonin levels are decreased in cardiovascular
diseases.50,51 Convincing evidence exists for the benefits of
increasing glucose uptake as an important therapeutic goal in the
management of left ventricular systolic dysfunction.52 Although
its role in melatonin-induced cardioprotection needs further
investigation, present data suggest that short-term melatonin
treatment in vivo, but not in vitro, improved basal glucose uptake
and insulin responsiveness in insulin-resistant cardiomyocytes
isolated from obese rats.
This study was supported by the South African National Research
Foundation, the Harry Crossley Foundation and Stellenbosch
University.
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