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Biomedical subjects

M Möhlig

Publications and source records attributed to M Möhlig.

At least 19 recordsLinked to original sources
PubMed2006

Adiponectin oligomers in human serum during acute and chronic exercise: relation to lipid metabolism and insulin sensitivity.

Beneficial effects of physical exercise include improved insulin sensitivity, which may be affected by a modulated release of adiponectin, which is exclusively synthesized in white adipose tissue and mediates insulin sensitivity. Adiponectin circulates in three different oligomers, which also have a distinct biological function. We therefore aimed to investigate the distribution of adiponectin oligomers in human serum in relation to physical activity. Thirty-eight lean and healthy individuals were investigated. Seven healthy women and 8 healthy men volunteered to investigate the effect of chronic exercise, at 3 different time points with different training intensities. These individuals were all highly trained and were compared to a control group with low physical activity (n = 15). For studying acute exercise effects, 8 healthy men participated in a bicycle test. Adiponectin was determined by ELISA, oligomers were detected by non-denaturating western blot. Total adiponectin and oligomers were unchanged by acute exercise. LDL cholesterol was significantly lower in the chronic exercise group (p = 0.03). Total adiponectin levels and oligomers were not different between these two groups and were unaltered by different training intensities. However, total adiponectin and specifically HMW oligomers correlated with HDL cholesterol (r = 0.459; p = 0.009). We conclude that acute and chronic exercise does not directly affect circulating adiponectin or oligomer distribution in lean and healthy individuals. Whether such regulation is relevant in individuals with a metabolic disorder remains to be determined. However, our data suggest that adiponectin oligomers have distinct physiological functions IN VIVO, and specifically HMW adiponectin is closely correlated with HDL cholesterol.

Adiponectin↗
PubMed2006

Arabinoxylan consumption decreases postprandial serum glucose, serum insulin and plasma total ghrelin response in subjects with impaired glucose tolerance.

OBJECTIVE: Arabinoxylan (AX) consumption is associated with metabolic improvement during diabetes and with modulation of ghrelin, an orexigenic gut hormone. The effect of AX consumption on ghrelin secretion in disturbed metabolic states is unknown. Therefore, we investigated the postprandial responses to AX consumption of serum glucose, insulin and triglycerides and plasma total and acylated ghrelin in subjects with impaired glucose tolerance (IGT). DESIGN: Randomized, single-blind, controlled, crossover intervention trial. SUBJECTS: Seven female and four male adults with IGT, aged 55.5 years, and body mass index (BMI) 30.1 kg/m(2). INTERVENTION: Subjects received either placebo or 15 g AX supplement for 6 weeks with a 6-week washout period in-between. MAIN OUTCOME MEASUREMENTS: Postprandial responses of serum glucose, insulin and triglycerides, and plasma total and acylated ghrelin after a liquid meal challenge test (LMCT) measured at the beginning and at the end of the dietary intervention at -20, -5, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min. RESULTS: After LMCT, AX consumption resulted in lower postprandial responses in serum glucose, insulin and triglycerides (P<0.05). Compared to placebo, total plasma ghrelin was also reduced by 42+/-8 pg/ml (P<0.001) after AX consumption with no difference in plasma acylated ghrelin. CONCLUSION: AX consumption improved postprandial metabolic responses after an LMCT in subjects with IGT and reduced total ghrelin response. However, acylated ghrelin responses were unchanged, suggesting that the acylated ghrelin-mediated orexigenic regulation is not improved as only total plasma ghrelin decreased.

Aged↗
PubMed2006

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling.

AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. MATERIALS AND METHODS: Consecutive PCOS patients (n=118) with fasting glucose <6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >/=7.8 mmol/l) from those with NGT. RESULTS: According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. CONCLUSIONS/INTERPRETATION: Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.

Adult↗
PubMed2006

Glucagon suppression of ghrelin secretion is exerted at hypothalamus-pituitary level.

CONTEXT: The mechanisms underlying the well-known glucagon-induced satiety effect are unclear. Recently, we showed that glucagon induces a remarkable decrease in the orexigenic hormone ghrelin that might be responsible for this effect. OBJECTIVE: The objective of this study was to evaluate the putative role of the hypothalamic pituitary axis in glucagon's suppressive effect on ghrelin secretion. DESIGN, SUBJECTS, AND METHODS: Prospectively, we studied the endocrine and metabolic responses to im glucagon administration in 22 patients (16 males; age, 21-68 yr; body mass index, 28.1 +/- 1.1 kg/m(2)) with a known hypothalamic-pituitary lesion and at least one pituitary hormone deficiency. Control experiments were performed in 27 healthy subjects (15 males; age, 19-65 yr; body mass index, 25.5 +/- 0.9 kg/m(2)). RESULTS: The suppression of ghrelin by glucagon measured as area under the curve(240 min) was significantly greater in controls when compared with patients (P < 0.01). Although there was a significant decrease in ghrelin in controls (P < 0.001), ghrelin was almost unchanged in patients (P = 0.359). Changes in glucagon, glucose, and insulin levels were comparable between both groups. CONCLUSIONS: We show that the hypothalamic-pituitary axis plays an essential role in the suppression of ghrelin induced by im glucagon administration. Glucagon significantly decreases ghrelin levels in healthy subjects. However, in the absence of an intact hypothalamic-pituitary axis, this effect was abolished. The mechanisms responsible for our observation are unlikely to include changes in glucose or insulin levels.

Adult↗
PubMed2006

Increase in serum resistin during weight loss in overweight subjects is related to lipid metabolism.

OBJECTIVE: Human resistin has been stated to influence preadipocyte cell numbers and to stimulate adipocyte triglyceride lipolysis in vivo and in vitro. However, its role in human obesity remains unclear. DESIGN: Cross-sectional study for comparisons of lean and obese subjects, and subsequent longitudinal 4-month weight loss intervention study in obese subjects. SUBJECTS: Healthy subjects, lean (n=20, BMI<25) and overweight (n=43, BMI>or=25). MEASUREMENTS: Serum resistin, body weight, body fat, waist-to-hip ratio, as well as markers of insulin resistance and lipid metabolism at baseline and after 4 months of intervention. RESULTS: Serum resistin was positively correlated to HOMA-IR (partial r=0.288; P=0.055), serum fructosamines (partial r=0.280; P=0.062), serum NEFA (partial r=0.276; P=0.066) and negatively to age (partial r=-0.349; P=0.019) and serum apolipoprotein A-1 (partial r=-0.363; P=0.014). During the intervention, serum resistin increased significantly (P<0.001). The increase was inversely related to changes in waist-to-hip ratio (P=0.025) and positively to serum apolipoprotein B (P=0.011). In males only, the increase in resistin during weight loss was predicted by total serum cholesterol at baseline (r=0.703, P=0.007). No relation was observed between changes in resistin and changes in HOMA-IR. CONCLUSION: The present study indicates an association between serum resistin and markers of abdominal fat distribution as well as the regulation of lipid metabolism. However, human resistin is unlikely to play an independent role in the regulation of glucose metabolism.

Adult↗
PubMed2006

Free fatty acids increase androgen precursors in vivo.

CONTEXT: There is considerable evidence that metabolic factors such as insulin resistance may induce hyperandrogenemia in polycystic ovary syndrome. However, other metabolic factors such as free fatty acids (FFAs) may also contribute to androgen excess. OBJECTIVE: The objective was to study effects of FFAs on adrenal production of androgen precursors in vivo. DESIGN AND PARTICIPANTS: We investigated eight healthy young men, because male individuals produce the androgen precursors dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione predominantly in the adrenal gland. A randomized controlled crossover trial was performed. INTERVENTION: After a 10-h overnight fast, 20% lipid/heparin or saline/heparin infusion was given at a rate of 1.5 ml/min. Four hours after start of lipid infusion, a euglycemic hyperinsulinemic clamp was performed. MAIN OUTCOME MEASURES: DHEA, androstenedione, 17-OH-progesterone, testosterone, estrone, LH, FSH, ACTH, and cortisol were measured. RESULTS: The adrenal androgen precursors DHEA and androstenedione showed a circadian decline during saline/heparin infusion (P < 0.05 vs. baseline, respectively), whereas no significant changes were observed during lipid/heparin infusion (P = not significant vs. baseline, respectively). Correspondingly, DHEA and androstenedione values were significantly elevated during lipid compared with saline infusion (P < 0.05, respectively), and areas under curve of both androgen precursors were significantly increased with lipid compared with saline infusion. Notably, all changes were detected before induction of insulin resistance. CONCLUSIONS: This study demonstrates that FFAs increase production of androgen precursors in vivo in men. These data tentatively suggest that hyperandrogenemia in polycystic ovary syndrome may be induced, at least in part, by elevated FFAs.

17-alpha-Hydroxyprogesterone↗
PubMed2006

Preliminary evidence of FABP2 A54T polymorphism associated with reduced risk of type 2 diabetes and obesity in women from a German cohort.

The T54 variant of the FABP2 gene has shown an association with the insulin resistance syndrome in some, but not all, studies. Here, we tested the hypothesis that the association between FABP2 A54T genotype and type 2 diabetes (T2DM) is confounded by body mass index (BMI) and is different between the two genders. 192 incident cases of T2DM and 384 sex- and age-matched controls were taken from the EPIC-Potsdam study cohort. Logistic regression analyses revealed that BMI was a strong confounder for diabetes risk association among women. When adjusted for BMI, the homozygous T54 variant was significantly associated with reduced risk of T2DM in women (OR = 0.24, 95 %CI: 0.07 - 0.82), but not in men in the co-dominant inheritance model. Accordingly, HbA (1c) values were significantly lower in women carrying two T54 alleles with BMI regarded as covariate. While accounting for potentially confounding effects, linear trends of increased BMI and leptin values were observed in women according to the presence of T54 alleles. The interaction term (p = 0.04) of continuous BMI and T54-coding genotypes suggested that the T54 variant is an effect-modifier for BMI in females. We conclude that the T54 allele of FABP2 A54T is associated both with higher BMI and reduced risk of T2DM in women from the German EPIC-Potsdam study.

Adult↗
PubMed2005

A dietary pattern protective against type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)--Potsdam Study cohort.

AIMS/HYPOTHESIS: The aim of this study was to identify a dietary pattern associated with diabetes-related biomarkers and to investigate whether this pattern is associated with the incidence of type 2 diabetes. METHODS: A nested case-control study of 192 cases of incident type 2 diabetes and 382 control subjects matched for sex and age was conducted. All subjects were participants in the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Dietary pattern score was derived using intake data on 48 food groups as exposure variables and the biomarkers HbA1c, HDL cholesterol, C-reactive protein and adiponectin as response variables in reduced rank regression. The association of the score with diabetes risk was estimated by conditional logistic regression analysis. RESULTS: A high score for the identified dietary pattern was characterised by a high intake of fresh fruit and a low intake of high-caloric soft drinks, beer, red meat, poultry, processed meat, legumes and bread (excluding wholegrain bread). Subjects with high scores had high plasma concentrations of HDL cholesterol and adiponectin and low plasma concentrations of HbA1c and C-reactive protein. After multivariate adjustment, the odds ratios for type 2 diabetes across increasing quintiles of the dietary pattern score were 1.0, 0.59, 0.51, 0.26 and 0.27, respectively (p = 0.0006 for trend). CONCLUSIONS/INTERPRETATION: A high score for the identified dietary pattern is associated with a more favourable biomarker profile and a substantially reduced incidence of type 2 diabetes.

Adiponectin↗
PubMed2005

[Significance of biomarkers for metabolic syndrome during weight reduction].

INTRODUCTION: Obesity is a risk factor for type 2 diabetes, hypertension, dyslipidemia and cardiovascular disease. We aimed to analyse the changes of parameters of the metabolic syndrome and to investigate which markers are useful in the prediction of a successful weight loss. Preliminary data of an ongoing study are presented. METHODS: 18 obese individuals (15 female, 3 male, mean age 50.9 years, mean BMI 36.1) finished a 12 month weight loss program. This weight loss program was based on a hypocaloric diet (50 % carbohydrates, 30 % fat, 20 % protein) and at least 60 min physical activity per week. At baseline, 6 months and 12 months physical examination, indirect calorimetry, bioimpedance analysis were performed and blood was taken for routine laboratory. An oral glucose tolerance test and an euglycemic hyperinsulinemic clamp (n = 13) were carried out at baseline and after 6 months. RESULTS: There was a decrease of the BMI (+/- SEM) from 36.1 +/- 1.3 to 33.4 +/- 1.2 after 6 months and 32.8 +/- 1.3 after 12 months. Waist circumference (-8.8 cm), fasting blood glucose (98.0 to 91.2 and 92.5 mg/dl) and HDL cholesterol (47.2 to 64.6 mg/dl after 12 months) improved significantly. Other parameters of the metabolic syndrome (blood pressure, lipids, insulin resistance) and adiponectin improved slightly, but changes failed to be significant. In a linear regression analysis age, insulin resistance (M-value) and adiponectin at baseline were significant and independent predictors of a successful weight loss. CONCLUSION: In conclusion, most parameters of the metabolic syndrome improved after successful weight reduction, although changes of most parameters were modest and did not reach statistical significance.

Adiponectin↗
PubMed2005

Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women.

OBJECTIVE: Obesity is linked to the insulin resistance syndrome (IRS), type 2 diabetes (T2D) and cardiovascular disease. Markers of chronic subclinical inflammation such as high-sensitive C-reactive protein (hs-CRP) and interleukin 6 (IL-6) are closely related to insulin resistance and obesity. Recent evidence suggests that adiponectin, a protein whose circulating levels are decreased in obesity, has anti-inflammatory properties, and also appears to enhance potently insulin action and therefore appears to function as a signal produced by adipose tissue that influences whole-body glucose metabolism. SUBJECTS AND METHODS: We investigated the cross-sectional and longitudinal association of adiponectin with CRP and IL-6 in 41 morbidly obese women with different stages of glucose tolerance before and 17 months after significant weight loss induced by gastric surgery. Adiponectin was measured by RIA. CRP and IL-6 were determined by commercially available ELISA systems. RESULTS: Weight loss induced a significant shift from T2D (preoperatively 34% vs postoperatively 2%) to impaired glucose tolerance (IGT) (37% preoperatively vs 30% postoperatively) and normal glucose tolerance (NGT) (29% preoperatively vs 68% postoperatively). Preoperatively adiponectin levels were negatively correlated with CRP (r=-0.59, P<0.0006), IL-6 (r=-0.42, P<0.02) and leukocytes (r=-0.41, P<0.007). After gastroplasty, adiponectin concentrations increased significantly (15.4+/-8.2 vs 19.8+/-6.2 microg/ml, P<0.005) associated with changes of weight and body mass index (r=-0.45, P<0.007; r=-0.35, P<0.04). Furthermore, preoperative CRP was significantly associated with changes in adiponectin even after adjustment for sex, age, preoperative body mass index (BMI) impaired glucose metabolism and changes in BMI and changes in BMI (standardized beta 0.61, P=0.005). CONCLUSION: Levels of adiponectin, which are associated with markers of chronic subclinical inflammation, could be significantly increased after weight loss in morbidly obese patients. This increase was more pronounced in patients with NGT compared to those with T2D and IGT. Preoperative levels of CRP are predictive for changes of adiponectin after weight loss.

Adiponectin↗
PubMed2005

Arabinoxylan-enriched meal increases serum ghrelin levels in healthy humans.

Soluble fibre like arabinoxylan (AX) is thought to have beneficial effects on metabolism. In this study, we investigated the effect of a breakfast enriched in AX fibre on glucose, insulin and ghrelin values. AX-enriched and control breakfasts were served to fifteen young volunteers (nine female, six male). Glucose, insulin and ghrelin responses were measured after the meal. To avoid effects from differences in glucose metabolism, further analysis was restricted to those subjects with known normal glucose regulation (seven female, four male). The AX fibre-enriched breakfast did not significantly change glucose levels for two hours after breakfast, but decreased insulin levels in the entire cohort (p = 0.035). Glucose response was also not significantly different in subjects with normal glucose regulation (p = 0.367), and the insulin responses after an AX-enriched breakfast showed only a tendency towards lower values (p = 0.065). Nevertheless, plasma ghrelin two hours after AX-enriched breakfast was higher than after the control meal (396.1 +/- 36.4 pg/ml vs. 328.3 +/- 32.6 pg/ml, p < 0.001). In subjects with normal glucose regulation, the AX-enriched breakfast increased ghrelin levels without any significant difference in glucose or insulin response. This effect is therefore unlikely to be mediated by insulin, but the underlying mechanism remains to be elucidated.

Adult↗
PubMed2005

In vivo activity of 11beta-hydroxysteroid dehydrogenase type 1 and free fatty acid-induced insulin resistance.

INTRODUCTION: Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), accompanied by elevated hepatic cortisol levels. METHODS: Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11beta-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11beta-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites. RESULTS: Lipid infusion increased FFAs (5.41 +/- 1.00 vs. 0.48 +/- 0.20 mmol/l; P < 0.005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6.02 +/- 2.60 vs. 4.08 +/- 2.15 mg/kg/min; P < 0.005]. After lipid and saline infusions no changes in 11beta-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5beta-tetrahydrocortisol (THF), 5alpha-THF, cortisone (THE), UFF/UFE and (5alpha-THF + THF)/THE ratios. CONCLUSIONS: We found no change in hepatic and whole-body 11beta-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11beta-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11beta-HSD1 is involved in other conditions of insulin resistance.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2005

Glucagon inhibits ghrelin secretion in humans.

OBJECTIVE: It is well known that i.m. glucagon administration stimulates GH and cortisol release in humans, although the mechanisms are unclear. These effects are similar to those described for ghrelin on somatotroph and corticotroph function. The aim of the present study was to investigate the role of ghrelin in mediating the stimulatory effects of glucagon and to evaluate the effect of glucagon on ghrelin secretion. DESIGN AND METHODS: We studied the endocrine and metabolic response to i.m. glucagon administration in 24 subjects (14 men, 10 women; age 19-65 years; body mass index, 25.3 +/- 1 kg/m(2)), who were shown to have an intact anterior pituitary function as evaluated before enclosure. RESULTS: Serum ghrelin concentrations fell significantly at 30, 60, 120 and 180 min after glucagon administration (means +/- s.e.m.; baseline, 377.9 +/- 34.5 pg/ml; nadir, 294.6 +/- 28.3 pg/ml (60 min); P < 0.01). Conversely, i.m. glucagon elicited an increase in GH (baseline, 1.5 +/- 0.4 microg/l; peak, 14.2 +/- 2.7 microg/l (180 min); P < 0.01) and cortisol concentrations (baseline, 452.6 +/- 35.2 nmol/l; peak, 622.1 +/- 44 nmol/l (180 min); P < 0.01). The changes in ghrelin concentration at both 120 and 180 min were still significant after correction for glucose and insulin (P < 0.05). CONCLUSIONS: We show that i.m. glucagon decreases ghrelin significantly. Therefore, the already known stimulatory effects of i.m. glucagon on cortisol and GH are not mediated by a change in ghrelin concentrations. The mechanisms underlying the ghrelin suppression after i.m. glucagon are unlikely to include glucose or insulin variations and need to be further elucidated.

Adult↗
PubMed2003

Post-prandial decrease of human plasma ghrelin in the absence of insulin.

Ghrelin is the most powerful orexigenic hormone in mammalian physiology. Ghrelin plasma concentrations increase prior to meal onset, but decrease post-prandially. We and others reported previously that insulin reduces circulating ghrelin levels and might therefore be a driving force for post-prandial suppression of ghrelin. To test the influence of insulin on post-prandial ghrelin regulation, a patient with Type I diabetes with complete insulin deficiency received a low glycemic index meal and subsequently an additional high glycemic index meal in the absence of insulin substitution. Subsequently, a sc injection of 0.08 IU Lispro insulin per kg body weight was given. Results were compared to those of a healthy control subject matched for sex, age and body mass index, which was undergoing the same test series (without Lispro bolus) in the presence of endogenous post-prandial insulin secretion. A substantial decrease of plasma ghrelin levels was observed in the insulin-deficient patient following low glycemic index carbohydrate load (27% plasma ghrelin decrease). The subsequent exposure to a high glycemic index meal resulted in a slight additional reduction of ghrelin levels (32% from baseline), while Lispro bolus did not induce further changes in circulating ghrelin (27% of baseline at termination). This post-prandial response was comparable to that of the healthy control subject (33% reduction after the first meal, 40% after the second meal). These data tentatively suggest that post-prandial secretion of ghrelin is not exclusively regulated by plasma insulin or plasma glucose but may depend on other metabolic factors yet to be identified.

Adult↗
PubMed2003

Ca2+/calmodulin-dependent protein kinase II delta2 regulates gene expression of insulin in INS-1 rat insulinoma cells.

Ca(2+)/calmodulin-dependent protein kinase II is a member of a broad family of ubiquitously expressed Ca(2+) sensing serine/threonine-kinases. Ca(2+)/calmodulin-dependent protein kinase II is highly expressed in insulin secreting cells and is associated with insulin secretory granules and has been proposed to play an important role in exocytosis or in insulin granule transport to release sites. To elucidate its function the antisense sequence of the major beta-cell subtype, Ca(2+)/calmodulin-dependent protein kinase II delta(2), was stably expressed in INS-1 rat insulinoma cells. This caused a loss of Ca(2+)/calmodulin-dependent protein kinase II delta(2) expression at the mRNA and protein level, while the expression of the 95% homologous Ca(2+)/calmodulin-dependent protein kinase II gamma and of beta-cell specific proteins such as the homeodomain factor pancreatic-duodenal homeobox factor-1 (PDX-1, also referred to as islet/duodenum homeobox-1, IDX-1, insulin promoter factor-1, IPF-1 and somatostatin transactivating factor-1, STF-1), the glucagon-like peptide-1 (GLP-1) receptor and K(ATP)-channels K(IR)6.2/SUR-1 (sulfonylurea receptor-1) was not altered. Unexpectedly, the cells showed a large reduction of insulin gene expression, which was due to reduced insulin gene transcription. Electrophoretic mobility shift assays of PDX-1 binding to the insulin promoter A1 and E2/A3A4 elements showed additional bands indicating alterations of PDX-1 complex formation. Stable over expression of Ca(2+)/calmodulin-dependent protein kinase II delta(2), by contrast, was associated with elevated expression of insulin mRNA. Therefore, we conclude that Ca(2+)/calmodulin-dependent protein kinase II delta(2) links fuel-dependent increases in intracellular Ca(2+) concentrations to transcriptional regulation of genes related to the metabolic control of insulin secretion.

ATP-Binding Cassette Transporters↗
PubMed2002

Euglycemic hyperinsulinemia, but not lipid infusion, decreases circulating ghrelin levels in humans.

The orexigenic and anabolic gastric hormone ghrelin is secreted in response to acute and chronic energy requirements. While pre-prandial increases and post-prandial decreases of plasma ghrelin levels in rodents and humans seem to indicate a role for the novel peptide hormone as an afferent meal initiator or "hunger hormone", the precise mechanisms which are suppressing ghrelin secretion in response to caloric intake remain largely unknown. We show here that human ghrelin levels decrease by almost 50% under hyperinsulinemic euglycemic clamp conditions (no.=4, p=0.001), revealing physiologically relevant increases of insulin levels as an independent determinant of circulating ghrelin levels. In a second study, 3-4-fold increased plasma free fatty acid levels, as another metabolic candidate for the modulation of circulating ghrelin concentrations, were generated by constant lipid infusion, but failed to change plasma ghrelin. Simultaneous elevation of free fatty acids and insulin again markedly decreased ghrelin concentration (no.=4, p=0.01). Insulin induced suppression of circulating ghrelin levels (or the lack thereof) could be a mechanism with relevance for the understanding of the (patho-) physiology of meal initiation and termination, the pathogenesis of the metabolic syndrome and for the development of respective therapeutic perspectives.

Adult↗