Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats

Abstract

We tested the hypothesis that long-term caffeine intake prevents the development of insulin resistance and hypertension in two pathological animal models: the high-fat (HF) and the high-sucrose (HSu) diet rat. We used six groups of animals: control; caffeine-treated (Caff; 1 g/l in drinking water during 15 d); HF; caffeine-treated HF (HFCaff); HSu; caffeine-treated HSu (HSuCaff). Insulin sensitivity was assessed using the insulin tolerance test. Blood pressure, weight gain, visceral fat, hepatic glutathione, plasma caffeine, insulin and NO, and serum NEFA and catecholamines were measured. Caffeine reversed insulin resistance and hypertension induced by both the HF and HSu diets. In the HF-fed animals caffeine treatment restored fasting insulin levels to control values and reversed increased weight gain and visceral fat mass. In the HSu group, caffeine reversed fasting hyperglycaemia and restored NEFA to control values. There were no changes either in plasma NO or in hepatic glutathione levels. In contrast, caffeine totally prevented the increase in serum catecholamines induced by HF and HSu diets. To test the hypothesis that inhibition of the sympathetic nervous system prevents the development of diet-induced insulin resistance we administered carvedilol, an antagonist of b1, b2 and also a1 adrenoceptors, to HF and HSu rats. Carvedilol treatment fully prevented diet-induced insulin resistance and hypertension, mimicking the effect of caffeine. We concluded that long-term caffeine intake prevented the development of insulin resistance and hypertension in HF and HSu models and that this effect was related to a decrease in circulating catecholamines.

Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity

“…We also have previously described (Conde et al 2012) that plasma concentrations of caffeine obtained with the dose 1 g/l are in the same range as those previously described in rats by Gasior et al (2002) and Cognato et al (2010) and correspond to a consumption of three to four cups of coffee per day in humans (Fredholm et al 1999).…”

“…Caffeine can acutely increase insulin secretion (Greenberg et al 2006), but the effects of sustained administration of the xanthine on insulin production by the pancreas appear to be, as many others, completely opposite from the ones observed after acute administration. We have previously shown that plasma insulin levels decrease after chronic caffeine treatment in hyperinsulinemic animal models of diet-induced insulin resistance (Conde et al 2012), although we could not ascertain the mechanism responsible for the lowering of plasma insulin induced by caffeine. It still remains to be clarified whether the hypoinsulinemic effect induced by chronic caffeine intake in insulin-resistant animal models is a direct effect of caffeine on the pancreas, possibly by the activation of AMPK (Long and Zierath 2006) or simply a negative feedback at the β cell ensuing improved peripheral insulin sensitivity.…”

“…This increase in endogenous glucose production associated with decreased skeletal muscle glucose uptake and decreased fatty acid oxidation (Young et al 1985;Acheson et al 2004;Mulder et al 2005) leads to hyperglycemia and tissue triglyceride deposition, major pathophysiological hallmarks of insulin resistance. We have recently shown that chronic caffeine intake prevents the development of insulin resistance and decreases circulating catecholamines in diet-induced insulin-resistant rats (Conde et al 2012). We have also shown that the pharmacological inhibition of the SNS with carvedilol, an antagonist of α1, β1, and β2 adrenoceptors, mimics the protective effect of caffeine, which suggests that chronic caffeine intake prevents dietinduced insulin resistance through a decrease in SNS activity.…”

“…The primary mechanism proposed for the protective role of caffeine in the development of type 2 diabetes was weight loss attributed to increased thermogenesis, lipolysis, and fat oxidation induced by this xanthine (Lopez-Garcia et al 2006;Van Dam et al 2006;Zheng et al 2004;Jeukendrup and Randell 2011) via sympathetic nervous system (SNS) activation (Dulloo et al 1992;Graham et al 2000). Nevertheless, this hypothesis remains controversial since several authors have shown that chronic coffee consumption does not cause significant weight reduction (Astrup et al 1992;Conde et al 2012). …”

Ingestão aguda de cafeína reduz a glicemia sanguínea antes e após o exercício físico agudo em ratos diabéticos

“…Its biological half-life varies from 2.5 to 4.5 hours Caffeine stimulates insulin secretion by pancreatic β-cells by increasing intracellular Ca 2+ 7 . In skeletal muscle caffeine can increase the expression of Glucose Transporter type 4 (GLUT4) by increasing intracellular Ca 2+ concentration and AMPK expression 7,8 . Caffeine also antagonizes the adenosine receptors involved in glycogenolysis and gluconeogenesis found in the cell membranes of hepatocytes 9 .…”