Blockade of the growth hormone (GH) receptor unmasks rapid GH-releasing peptide-6-mediated tissue-specific insulin resistance

The roles of GH and its receptor (GHR) in metabolic control are not yet fully understood. We studied the roles of GH and the GHR using the GHR antagonist pegvisomant for metabolic control of healthy nonobese men in fasting and nonfasting conditions. Ten healthy subjects were enrolled in a double blind, placebo-controlled study on the effects of pegvisomant on GHRH and GH-releasing peptide-6 (GHRP-6)-induced GH secretion before and after 3 days of fasting and under nonfasting conditions (n = 5). Under the condition of GHR blockade by pegvisomant in the nonfasting state, GHRP-6 (1 microg/kg) caused a increase in serum insulin (10.3 +/- 2.1 vs. 81.3 +/- 25.4 mU/L; P < 0.001) and glucose (4.2 +/- 0.3 vs. 6.0 +/- 0.6 mmol/L; P < 0.05) concentrations. In this group, a rapid decrease in serum free fatty acids levels was also observed. These changes were not observed under GHR blockade during fasting or in the absence of pegvisomant. We conclude that although these results were obtained from an acute study, and long-term administration of pegvisomant could render different results, blockade of the GHR in the nonfasting state induces tissue-specific changes in insulin sensitivity, resulting in an increase in glucose and insulin levels (indicating insulin resistance of liver/muscle), but probably also in an increase in lipogenesis (indicating normal insulin sensitivity of adipose tissue). These GHRP-6-mediated changes indicate that low GH bioactivity on the tissue level can induce changes in metabolic control, which are characterized by an increase in fat mass and a decrease in lean body mass. As a mechanism of these GHRP-6-mediated metabolic changes in the nonfasting state, direct nonpituitary-mediated GHRP-6 effects on the gastroentero-hepatic axis seem probable

Ghrelin drives GH secretion during fasting in man

OBJECTIVES: In humans, fasting leads to elevated serum GH concentrations. Traditionally, changes in hypothalamic GH-releasing hormone and somatostatin release are considered as the main mechanisms that induce this elevated GH secretion during fasting. Ghrelin is an endogenous ligand of the GH secretagogue receptor and is synthesized in the stomach. As ghrelin administration in man stimulates GH release, while serum ghrelin concentrations are elevated during fasting in man, this increase in ghrelin levels might be another mechanism whereby fasting results in stimulation of GH release. DESIGN AND SUBJECTS: In ten healthy non-obese males we performed a double-blind placebo-controlled crossover study comparing fasting with and fasting without GH receptor blockade. GH, ghrelin, insulin, glucose and free fatty acids were assessed. RESULTS: While ghrelin levels do not vary considerably in the fed state, fasting rapidly induced a diurnal rhythm in ghrelin concentrations. These changes in serum ghrelin concentrations during fasting were followed by similar, profound changes in serum GH levels. The rapid development of a diurnal ghrelin rhythm could not be explained by changes in insulin, glucos

Diabetes in patients with acromegaly treated with pegvisomant: observations from acrostudy

Purpose: To explore the effects of pegvisomant (PEGV) on glucose metabolism in patients with acromegaly within ACROSTUDY, an international, observational, prospective safety surveillance study. Methods: Patients were retrospectively divided into two cohorts, with (DM group) or without diabetes mellitus (no-DM). Parameters of glucose metabolism and IGF-I values were analyzed yearly both cross-sectionally for 4 years (yrs) and longitudinally at 1 and 4–5 yrs of PEGV treatment. Results: Among 1762 patients, 510 (28.9%) had DM before PEGV start. At cross-sectional analyses, in the DM group mean blood glucose was 140.0 ± 58.7 mg/dl at baseline, 116.4 ± 44.8 mg/dl at year 1 and 120.0 ± 44.3 mg/dl at yr 4. Mean HbA1c was 6.6 ± 1.2 % at yr 1 vs. 7.0 ± 1.4 % at baseline. HbA1c was above 6.5% in 61.9% at baseline and ranged from 45.4 to 53.8% at subsequent yearly time points. At the 4-yr longitudinal analysis, in the DM group (n = 109), mean blood glucose decreased by 20.2 mg/dl at yr 4, mean HbA1c was 7.0 ± 1.5% at baseline vs. 6.8 ± 1.4%. Patients achieved IGF-I normalization in 52.1% and 57.4% of cases in the DM and no-DM groups, respectively at 1 year. The mean daily PEGV dose (mg/day) was higher in the DM group (18.2 vs. 15.3) while the absolute change of IGF-I values from baseline was similar in both groups. PEGV was well tolerated in both groups without any unexpected AEs. Conclusions: Patients with DM had a moderate decrease in mean fasting glucose values during PEGV treatment

Voice-Based Marketing for Agricultural Products: A Case Study in Rural Northern Ghana

We present a study conducted in rural Northern Ghana about issues around the marketing of agricultural products and the need of mobile-based ICT solutions. The need for the spread of information and web access to communities in developing countries has given rise to the design and development of numerous ICT solutions, many of which have focused on the recent increase of mobile usage in developing countries. The contributions of this paper are: 1) Empirical results from a field survey run in Northern Ghana, which points to issues of a lack of buyers, low price offers and lack of transportation to sale points as the main issues in marketing of agricultural products and also points to the potential for mobile-based ICT solutions to mitigate the pertinent issues within the case study, but also in other areas. 2) The development of a voice-based prototype that allows medium to large-scale farmers in rural areas to place advertisements on the World Wide Web. The prototype was evaluated based on functionality and feasibility, including financial sustainability

[Dengue and chikungunya acquired during travel in the tropics]

Item does not contain fulltext- The global incidence of dengue and chikungunya has greatly increased over recent decades, partly due to the increase of geographic distribution of both vectors.- These infections are endemic to the tropics and subtropics, however autochthonous transmission and outbreaks have been described in non-endemic areas.- Currently, there is a large chikungunya outbreak in the western hemisphere which started in the Caribbean. Chikungunya had not previously been endemic to this region.- Both arboviral infections are important causes of fever in Dutch travellers retuning from tropical destinations.- The clinical presentations of dengue and chikungunya overlap; both are characterised by high fever and arthralgia. Bleeding and plasma leakage are potentially life-threatening complications of dengue, while persistent arthralgia typifies chikungunya.- The prevention of mosquito bites, by using protective clothing and insect repellents, is the only way to prevent infection. No vaccine is yet available

A Dialogue with Linked Data: Voice-based Access to Market Data in the Sahel

The Linked Data movement has facilitated efficient data sharing in many domains. However, people in rural developing areas are mostly left out. Lack of relevant content and suitable interfaces prohibit potential users in rural communities to produce and consume Linked Data. In this paper, we present a case study exposing locally produced market data as Linked Data, which shows that Linked Data can be meaningful in a rural, development context. We present a way of enriching the market data with voice labels, allowing for the development of applications that (re-)use the data in voice-based applications. Finally, we present a prototype demonstrator that provides access to this linked market data through a voice interface, accessible to first generation mobile phones