Relationships between Desacylated and Acylated Ghrelin and Insulin Sensitivity in the Metabolic Syndrome

Barazzoni, Rocco; Zanetti, Michela; Ferreira, Clara; Vinci, Pierandrea; Pirulli, A.; Mucci, M.; Dore, Franca; Fonda, M.; Ciocchi, Beniamino; Cattin, Luigi; Guarnieri, Gianfranco

doi:10.1210/jc.2006-2527

Cited by 211 publications

(216 citation statements)

References 25 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…[2][3][4] However, the potential differences between the different ghrelin forms under these pathophysiological conditions are controversial and remain largely undefined. [34][35][36][37][38] As expected, our data show decreased plasma desacyl ghrelin levels in obese patients, which is in accordance with studies carried out by other authors. [34][35][36][37][38] Nonetheless, we found, for the first time, that plasma acylated ghrelin levels are increased in obesity and obesity-associated T2D.…”

Section: Discussionsupporting

confidence: 92%

“…[34][35][36][37][38] As expected, our data show decreased plasma desacyl ghrelin levels in obese patients, which is in accordance with studies carried out by other authors. [34][35][36][37][38] Nonetheless, we found, for the first time, that plasma acylated ghrelin levels are increased in obesity and obesity-associated T2D. The elevation of circulating acylated ghrelin concentrations in obese individuals may play a role in obesity-associated hyperphagia and adiposity.…”

Section: Discussionsupporting

confidence: 92%

“…Increased levels of acylated ghrelin have also been related to hyperglycemia, hyperinsulinemia and the degree of insulin resistance, which is in accordance with data published by other authors. 34,40 Insulin infusion at pharmacological doses (resulting in serum insulin levels of 1200 pmol l À1 ) throughout a 120 min euglycemic-hyperinsulinemic clamp decreased acylated ghrelin in patients with T2D. 41 Similar suppression of plasma acylated ghrelin has been observed in insulinsensitive vs insulin-resistant obese subjects infused with supraphysiological doses of insulin (75 mU m 2 min) throughout 180-min clamps.…”

Section: Discussionmentioning

confidence: 79%

See 2 more Smart Citations

Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

et al. 2009

View full text Add to dashboard Cite

Objectives: The orexigenic hormone ghrelin circulates mainly in two forms, acylated and desacyl ghrelin. We evaluated the impact of obesity and obesity-associated type 2 diabetes (T2D) on ghrelin forms and the potential role of acylated and desacyl ghrelin in the control of adipogenesis in humans. Methods: Plasma concentrations of the different ghrelin forms were measured in 80 subjects. The expression of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) was analyzed in omental adipose tissue using western blot and immunohistochemistry, and the effect of acylated ghrelin and desacyl ghrelin (0.1-1000 pmol l À1 ) on adipogenesis was determined in vitro in omental adipocytes. Results: Circulating concentrations of acylated ghrelin were increased, whereas desacyl ghrelin levels were decreased, in obesity and obesity-associated T2D. Body mass index, waist circumference, insulin and HOMA (homeostasis model assessment) index were positively correlated with acylated ghrelin levels. Obese individuals showed a lower protein expression of GHS-R in omental adipose tissue. In differentiating omental adipocytes, incubation with both acylated and desacyl ghrelin significantly increased PPARg (peroxisome proliferator-activated receptor g) and SREBP1 (sterol-regulatory element binding protein-1) mRNA levels, as well as several fat storage-related proteins, including acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase and perilipin. Consequently, both the ghrelin forms stimulated intracytoplasmatic lipid accumulation. Conclusions: Both acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Given the lipogenic effect of acylated ghrelin on visceral adipocytes, the herein-reported elevation of its circulating concentrations in obese individuals may play a role in excessive fat accumulation in obesity.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 79%

See 1 more Smart Citation

Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

et al. 2009

View full text Add to dashboard Cite

show abstract

“…We found that ghrelin concentrations of patients with type 2 diabetes was significantly lower (P<0.05) than those of controls group which was in line with previous studies [7,[15][16][17]. Our findings support the view that low ghrelin level could have a causative role in the development of type 2 diabetes.…”

Section: Ghrelin Concentrations In the Studied Groupssupporting

confidence: 92%

The Relationship between Type 2 Diabetes and Total Ghrelin Level in a Population Sample in the United Arab Emirates

Farajallah¹,

Ahmed²,

Abdullah³

et al. 2014

iosrphr

View full text Add to dashboard Cite

“…Moreover, insulin-resistant obese subjects have an elevated AG:DAG ratio when compared with insulin-sensitive obese subjects (10,11,12). These findings suggest that the inhibition of ghrelin might be beneficial for glycemic control and body composition.…”

Section: Introductionmentioning

confidence: 85%

Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?

Özcan¹,

Neggers²,

Miller³

et al. 2014

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: The objective of this study was to assess the effects of a continuous overnight infusion of des-acyl ghrelin (DAG) on acylated ghrelin (AG) levels and glucose and insulin responses to a standard breakfast meal (SBM) in eight overweight patients with type 2 diabetes. Furthermore, in the same patients and two additional subjects, the effects of DAG infusion on AG concentrations and insulin sensitivity during a hyperinsulinemic-euglycemic clamp (HEC) were assessed. Research design and methods: A double-blind, placebo-controlled cross-over study design was implemented, using overnight continuous infusions of 3 and 10 mg DAG/kg per h and placebo to study the effects on a SBM. During a HEC, we studied the insulin sensitivity. Results: We observed that, compared with placebo, overnight DAG administration significantly decreased postprandial glucose levels, both during continuous glucose monitoring and at peak serum glucose levels. The degree of improvement in glycemia was correlated with baseline plasma AG concentrations. Concurrently, DAG infusion significantly decreased fasting and postprandial AG levels. During the HEC, 2.5 h of DAG infusion markedly decreased AG levels, and the M-index, a measure of insulin sensitivity, was significantly improved in the six subjects in whom we were able to attain steady-state euglycemia. DAG administration was not accompanied by many side effects when compared with placebo. Conclusions: DAG administration improves glycemic control in obese subjects with type 2 diabetes through the suppression of AG levels. DAG is a good candidate for the development of compounds in the treatment of metabolic disorders or other conditions with a disturbed AG:DAG ratio, such as type 2 diabetes mellitus or Prader-Willi syndrome.

show abstract

Relationships between Desacylated and Acylated Ghrelin and Insulin Sensitivity in the Metabolic Syndrome

Abstract: Obesity could alter circulating ghrelin profile, and relative A-Ghr excess could contribute to obesity-associated insulin resistance in metabolic syndrome.

Cited by 211 publications

References 25 publications

Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

The Relationship between Type 2 Diabetes and Total Ghrelin Level in a Population Sample in the United Arab Emirates

Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?

Contact Info

Product

Resources

About