Low Plasma Ghrelin Is Associated With Insulin Resistance, Hypertension, and the Prevalence of Type 2 Diabetes

Abstract

Experimental studies have suggested that ghrelin plays a role in glucose homeostasis and in the regulation of blood pressure (BP). We therefore assessed the hypothesis that a low ghrelin concentration may be a risk factor for type 2 diabetes and hypertension. We also characterized the effect of the ghrelin Arg51Gln and Leu72Met mutations on ghrelin concentrations in the population-based hypertensive (n ‫؍‬ 519) and control (n ‫؍‬ 526) cohorts of our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. The fasting plasma ghrelin concentrations of 1,040 subjects were analyzed using the radioimmunoassay method. Insulin sensitivity was assessed using the quantitative insulin sensitivity check index (QUICKI). Ghrelin concentrations were negatively associated with fasting insulin (P < 0.001), systolic (P ‫؍‬ 0.026) and diastolic BP (P ‫؍‬ 0.018), and the prevalence of type 2 diabetes (P ‫؍‬ 0.015) and insulin resistance (P < 0.001) in the multivariate models. In the control cohort, low ghrelin was associated with hypertension (BP >140/90 mmHg) (P ‫؍‬ 0.031). The subjects with the ghrelin 51Gln allele had lower ghrelin concentrations than the Arg51Arg homozygotes (P ‫؍‬ 0.001). We conclude that low ghrelin is independently associated with type 2 diabetes, insulin concentration, insulin resistance, and elevated BP. Therefore, it might have some role in the etiology of type 2 diabetes and the regulation of BP. The ghrelin Arg51Gln mutation is associated with low plasma ghrelin concentrations. Diabetes 52:2546 -2553, 2003 G hrelin is a recently discovered peptide hormone secreted mainly from the stomach (1). It has a very potent growth hormone (GH)-releasing effect both in animal models and humans (1-3). In addition, it probably has effects independent of GH secretion (4). It is a somatotrophic orexigenic adipogenic hormone that links the regulatory systems for growth and energy balance (5). The effects of ghrelin are mediated through the GH secretagogue receptor, which is widely distributed in the body (6).The role of ghrelin in glucose and insulin metabolism has been studied actively. In experimental settings, glucose administration or food intake have been shown to decrease plasma ghrelin concentrations (7-9). Studies of the effects of ghrelin on insulin secretion have shown both stimulatory (10 -12) and inhibitory effects (13,14). In human subjects, insulin infusion has been shown to decrease ghrelin concentrations (15,16), whereas parenteral administration of insulin had no effect on ghrelin concentrations (17). On contrary, administration of insulin and leptin induced the increase of ghrelin mRNA in rats (18).Ghrelin exerts beneficial hemodynamic effects in humans by reducing cardiac afterload and increasing cardiac output (19). The vasodilatory effect is possibly mediated through a GH/IGF-I/nitric oxide-independent mechanism (20).Based on these recent studies, it appears that ghrelin might have a role in glucose and insulin metabolism and it also may influence blood pressure (BP) levels. Therefore, chang...

Ghrelin in obesity and endocrine diseases

“…Obese subjects with the Arg51Gln variant had lower body weights than obese subjects with the wild-type Arg51Arg variant (Ukkola et al, 2001). Although studies A c c e p t e d M a n u s c r i p t 13 have showed correlation between Arg51Gln and lower ghrelin levels (Poykko et al, 2003;Ukkola et al, 2002), another study was unable to confirm this finding (Vivenza et al, 2004).…”

Evaluation and Diagnostic Potential of Serum Ghrelin in Feline Hypersomatotropism and Diabetes Mellitus

“…This study suggests that, in parallel to the situation in man,10, 11, 12, 18, 19 serum ghrelin is suppressed in cats with HS‐induced DM and in cats with DM unrelated to HS. Serum ghrelin is therefore not useful as a diagnostic for determining the presence or absence of HS in the diabetic cat.…”

Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats

“…In addition, ghrelin may be a useful treatment for diabetes. Recently, circulating ghrelin levels were discovered to be decreased in patients with type 2 diabetes [37]. Ghrelin activity is involved in insulin resistance as well as the maintenance of energy balance [37].…”

“…Recently, circulating ghrelin levels were discovered to be decreased in patients with type 2 diabetes [37]. Ghrelin activity is involved in insulin resistance as well as the maintenance of energy balance [37]. As multiple studies have demonstrated the importance of ghrelin in glucose and insulin metabolism [2,3], ghrelin will be an important molecule to investigate the pathophysiology of diabetes.…”