Hormonal Regulators
Insulin
Insulin is thought to be a major regulator of circulating Ghrelin. Reciprocal changes of the two have been fairly consistently demonstrated in humans although rat studies have shown contradictions. But type1 diabetics given meals and type 2 diabetic patients given low dose glucose IV suppressed their Ghrelin despite no detectable insulin levels or insulin rise respectively! Insulin decreased Ghrelin levels in normal humans but to a lesser extent only in type 2 diabetics. Eur J Endocrinol. 2003 Nov;149(5):403-6. . Insulin infusion (euglycemic hyperinsulinaemic clamp) in 35 patients with uncomplicated obesity suppressed Ghrelin levels, with suppression being directly proportional to the insulin sensitivity. Regul Pept. 2004 Nov 15;122(3):179-83
The effect of gastrointestinal hormones and insulin on Ghrelin secretion in isolated rat stomach has been assessed during vagal prestimulation. This model offers the advantage of avoiding systemic interactions. GLP-1 decreased Ghrelin secretion significantly. Insulin, gastrin and somatostatin also significantly inhibited Ghrelin secretion. In contrast, GIP augmented both pre-stimulated and basal Ghrelin secretion. Regul Pept. 2004 Jun 15;119(1-2):93-8.
A further study was undertaken to investigate whether insulin was the predominant regulator of Ghrelin. Obese subjects with and without insulin resistance and similar glycaemic levels (steady-state glucose levels) were assessed for Ghrelin levels in the fasting state. Fasting insulin concentrations were clearly higher in the insulin resistant subjects who had lower Ghrelin levels compared to insulin sensitive obese patients. The study shows that Ghrelin concentration is inversely related to insulin resistance and hyperinsulinism rather than glucose levels. J Clin Endocrinol Metab. 2004 Apr;89(4):1630-5. Another study in obese subjects using DEXA scanning for body composition and the euglycemic hyperinsulinaemic clamp demonstrated that Ghrelin level changes were predominantly determined by fat mass rather than metabolic syndrome features (hypertension and HDL levels). Metabolism. 2003 Nov;52(11):1460-3.
Intravenous glucose administration in 7 healthy control subjects and 8 T2DM subjects compared Ghrelin responses in the first 10 minutes, taking advantage of the fact that type 2 diabetics are unable to mount a significant first phase response of insulin secretion. In the first ten minutes of this study, no insulin response occurred in the type 2 diabetics. This group attained higher glucose levels with equal Ghrelin decreases as the normal controls with higher insulin response. Eur J Endocrinol. 2003 Nov;149(5):403-6 This could suggest a regulation of Ghrelin independent of insulin and probably more dependent on glucose, at least in the early phases of meal ingestion.
At 2 and 12 months post Biliopancreatic diversion (BPD) surgery for obesity, body weight and BMI dropped sharply, with a reduction in insulin resistance (HOMA IR), as well as serum Leptin concentration. But serum Ghrelin levels increased significantly at 12 months, when food intake had returned to preoperative levels. The negative relationship observed between post-BPD changes in HOMA IR values and changes in serum Ghrelin concentration is suggested as supporting the assumption of the role of insulin in the modulation of Ghrelin production. Obes Res. 2004 Apr;12(4):684-7
PYY an intestinal hormone which suppresses appetite, has been shown to suppress Ghrelin levels with satiety induction. N Engl J Med. 2003 Sep 4;349(10):941-8.
Leptin has variable effects on Ghrelin levels and does not seem to be a regulator of Ghrelin. Leptin deficient states (humans or rodents with absent Leptin signaling due to inactivating mutations in ligand or its receptor) show low Ghrelin levels with obesity (similar to obese individuals with intact Leptin signalling). Conversely, increased circulating Leptin (achieved either transgenically or by peripheral injections) produces animals that are lean and shows increased Ghrelin expression. These 2 examples show that Ghrelin tracks alteration in body weight rather than Leptin.
A study of 120 healthy men and women revealed that Ghrelin levels were inversely related to Leptin and Central adiposity and not related to total energy intake. A three-day Fast abolished the meal related Ghrelin secretion patterns with low Leptin levels and no significant change in fat mass. Recombinant Leptin administration did not regulate Ghrelin levels in the short-term (several hours to a few days ). Overall it may well be that Leptin and Ghrelin function independently of each other in healthy humans. J Clin Endocrinol Metab. 2004 Jan;89(1):335-43
A study assessing the response of fasting and postprandial total Ghrelin to short-term energy restriction found that with short-term energy restriction without change in fat mass, fasting and postprandial total Ghrelin levels do not change despite a significant reduction in Leptin levels J Clin Endocrinol Metab. 2004 Apr;89(4):1727-32.
Omeprazole treatment for 10 weeks in rats did not change Ghrelin levels, nor did a 2 day infusion of gastrin. These make Gastrin an unlikely candidate in Ghrelin secretion regulation. Regul Pept. 2001 Jun 15;99(2-3):141-50
Insulin is thought to be a major regulator of circulating Ghrelin. Reciprocal changes of the two have been fairly consistently demonstrated in humans although rat studies have shown contradictions. But type1 diabetics given meals and type 2 diabetic patients given low dose glucose IV suppressed their Ghrelin despite no detectable insulin levels or insulin rise respectively! Insulin decreased Ghrelin levels in normal humans but to a lesser extent only in type 2 diabetics. Eur J Endocrinol. 2003 Nov;149(5):403-6. . Insulin infusion (euglycemic hyperinsulinaemic clamp) in 35 patients with uncomplicated obesity suppressed Ghrelin levels, with suppression being directly proportional to the insulin sensitivity. Regul Pept. 2004 Nov 15;122(3):179-83
The effect of gastrointestinal hormones and insulin on Ghrelin secretion in isolated rat stomach has been assessed during vagal prestimulation. This model offers the advantage of avoiding systemic interactions. GLP-1 decreased Ghrelin secretion significantly. Insulin, gastrin and somatostatin also significantly inhibited Ghrelin secretion. In contrast, GIP augmented both pre-stimulated and basal Ghrelin secretion. Regul Pept. 2004 Jun 15;119(1-2):93-8.
A further study was undertaken to investigate whether insulin was the predominant regulator of Ghrelin. Obese subjects with and without insulin resistance and similar glycaemic levels (steady-state glucose levels) were assessed for Ghrelin levels in the fasting state. Fasting insulin concentrations were clearly higher in the insulin resistant subjects who had lower Ghrelin levels compared to insulin sensitive obese patients. The study shows that Ghrelin concentration is inversely related to insulin resistance and hyperinsulinism rather than glucose levels. J Clin Endocrinol Metab. 2004 Apr;89(4):1630-5. Another study in obese subjects using DEXA scanning for body composition and the euglycemic hyperinsulinaemic clamp demonstrated that Ghrelin level changes were predominantly determined by fat mass rather than metabolic syndrome features (hypertension and HDL levels). Metabolism. 2003 Nov;52(11):1460-3.
Intravenous glucose administration in 7 healthy control subjects and 8 T2DM subjects compared Ghrelin responses in the first 10 minutes, taking advantage of the fact that type 2 diabetics are unable to mount a significant first phase response of insulin secretion. In the first ten minutes of this study, no insulin response occurred in the type 2 diabetics. This group attained higher glucose levels with equal Ghrelin decreases as the normal controls with higher insulin response. Eur J Endocrinol. 2003 Nov;149(5):403-6 This could suggest a regulation of Ghrelin independent of insulin and probably more dependent on glucose, at least in the early phases of meal ingestion.
At 2 and 12 months post Biliopancreatic diversion (BPD) surgery for obesity, body weight and BMI dropped sharply, with a reduction in insulin resistance (HOMA IR), as well as serum Leptin concentration. But serum Ghrelin levels increased significantly at 12 months, when food intake had returned to preoperative levels. The negative relationship observed between post-BPD changes in HOMA IR values and changes in serum Ghrelin concentration is suggested as supporting the assumption of the role of insulin in the modulation of Ghrelin production. Obes Res. 2004 Apr;12(4):684-7
PYY an intestinal hormone which suppresses appetite, has been shown to suppress Ghrelin levels with satiety induction. N Engl J Med. 2003 Sep 4;349(10):941-8.
Leptin has variable effects on Ghrelin levels and does not seem to be a regulator of Ghrelin. Leptin deficient states (humans or rodents with absent Leptin signaling due to inactivating mutations in ligand or its receptor) show low Ghrelin levels with obesity (similar to obese individuals with intact Leptin signalling). Conversely, increased circulating Leptin (achieved either transgenically or by peripheral injections) produces animals that are lean and shows increased Ghrelin expression. These 2 examples show that Ghrelin tracks alteration in body weight rather than Leptin.
A study of 120 healthy men and women revealed that Ghrelin levels were inversely related to Leptin and Central adiposity and not related to total energy intake. A three-day Fast abolished the meal related Ghrelin secretion patterns with low Leptin levels and no significant change in fat mass. Recombinant Leptin administration did not regulate Ghrelin levels in the short-term (several hours to a few days ). Overall it may well be that Leptin and Ghrelin function independently of each other in healthy humans. J Clin Endocrinol Metab. 2004 Jan;89(1):335-43
A study assessing the response of fasting and postprandial total Ghrelin to short-term energy restriction found that with short-term energy restriction without change in fat mass, fasting and postprandial total Ghrelin levels do not change despite a significant reduction in Leptin levels J Clin Endocrinol Metab. 2004 Apr;89(4):1727-32.
Omeprazole treatment for 10 weeks in rats did not change Ghrelin levels, nor did a 2 day infusion of gastrin. These make Gastrin an unlikely candidate in Ghrelin secretion regulation. Regul Pept. 2001 Jun 15;99(2-3):141-50