Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels

Lindqvist, Andreas; Shcherbina, Liliya; Prasad, Rashmi B.; Miskelly, Michael G.; Abels, Mia; Martínez-López, José A; Fred, Rikard G.; Nergård, Bent Johnny; Hedenbro, Jan; Groop, Leif; Hjerling-Leffler, Jens; Wierup, Nils

doi:10.1016/j.mce.2020.110835

Cited by 36 publications

(30 citation statements)

References 24 publications

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“…However, interestingly, here we show, for the first time, the positive effects of single D-Pinitol intake on ghrelin levels, and this result is specific for this hormone. It is known that ghrelin inhibits the secretion of insulin in pancreatic β cells [34,42]. Further investigation is needed to decipher the mechanism of action of D-Pinitol on beta cells, to inhibit insulin secretion, as shown in our experiments with INS-1, but it is also plausible that the increase in ghrelin levels under oral D-Pinitol contributes for the transient decrease in insulin levels detected in the plasma of rats receiving a single dose of D-Pinitol.…”

Section: Discussionmentioning

confidence: 80%

D-Pinitol from Ceratonia siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

et al. 2020

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To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analyzed its oral pharmacokinetics and its effects on (a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), (b) insulin signaling in the liver and (c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associated with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation, while sustaining glycaemia through the liver-based mechanisms of glycolysis control.

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Section: Discussionmentioning

confidence: 80%

D-Pinitol from Ceratonia siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

et al. 2020

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show abstract

“…But, interestingly, here we show for the first time the positive effects of single D-Pinitol intake on ghrelin levels and this result is specific for this hormone. It is known that ghrelin inhibits the secretion of insulin in pancreatic β cells [34,42]. Further investigation is needed to decipher the mechanism of action of D-Pinitol on beta cells to inhibit insulin secretion as shown in our experiments with INS-1, but it is also plausible that the increase in ghrelin levels under oral D-Pinitol contributes for the transient decrease in insulin levels detected in the plasma of rats receiving a single dose of D-Pinitol.…”

Section: Discussionmentioning

confidence: 81%

D-Pinitol from Ceratonia Siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

Navarro

Decara

Medina-Vera

et al. 2020

Preprint

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To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analysed its oral pharmacokinetics and its effects on a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), b) insulin signaling in the liver and c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associate with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation while sustaining glycaemia through liver-based mechanisms of glycolysis control.

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“…Regarding the role of ghrelin in the pathophysiology of obesity, available case reports have shown that individuals with ghrelinoma are overweight or obese, 39‐41 and although these neuroendocrine tumours are very rare, and available information is scarce, 39‐41 it is plausible the hyperghrelinaemia, observed in these patients, plays a role in the development of obesity. Furthermore, research has shown that ghrelin influences glucose homoeostasis by directly increasing glycaemia, 42 decreasing pancreatic insulin secretion 43 and plasma insulin levels, 44 as well as decreasing insulin sensitivity in humans 45 . Additionally, considering the accelerating effect of ghrelin on gastric emptying, 46 ghrelin injections may increase postprandial glycaemia indirectly 46 .…”

Section: The Ghrelin Systemmentioning

confidence: 99%

The regulation of gastric ghrelin secretion

Nunez‐Salces

Feinle‐Bisset

et al. 2020

Acta Physiologica

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Ghrelin is a gastric hormone with multiple physiological functions, including the stimulation of food intake and adiposity. It is well established that circulating ghrelin levels are closely associated with feeding patterns, rising strongly before a meal and lowering upon food intake. However, the mechanisms underlying the modulation of ghrelin secretion are not fully understood. The purpose of this review is to discuss current knowledge on the circadian oscillation of circulating ghrelin levels, the neural mechanisms stimulating fasting ghrelin levels and peripheral mechanisms modulating postprandial ghrelin levels. Furthermore, the therapeutic potential of targeting the ghrelin pathway is discussed in the context of the treatment of various metabolic disorders, including obesity, type 2 diabetes, diabetic gastroparesis and Prader‐Willi syndrome. Moreover, eating disorders including anorexia nervosa, bulimia nervosa and binge‐eating disorder are also discussed.

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Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels

Cited by 36 publications

References 24 publications

D-Pinitol from Ceratonia siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

D-Pinitol from Ceratonia siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

D-Pinitol from Ceratonia Siliqua Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats

The regulation of gastric ghrelin secretion

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