123 research outputs found
LEAP2 changes with body mass and food intake in humans and mice
Acyl-ghrelin administration increases food intake, body weight, and blood glucose. In contrast, mice lacking ghrelin or ghrelin receptors (GHSRs) exhibit life-threatening
hypoglycemia during starvation-like conditions but do not consistently exhibit overt metabolic phenotypes when given ad libitum food access. These results, and findings of
ghrelin resistance in obese states, imply nutritional state-dependence of ghrelin’s metabolic actions. Here, we hypothesized that LEAP2 (liver enriched antimicrobial
peptide-2), a recently-characterized endogenous GHSR antagonist, blunts ghrelin action during obese states and post-prandially. To test this hypothesis, we determined
changes in plasma LEAP2 and acyl-ghrelin due to fasting, eating, obesity, Roux-en-Y gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), oral glucose administration,
and type 1 diabetes mellitus (T1DM) using humans and/or mice. Our results suggest that plasma LEAP2 is regulated by metabolic status: its levels increase with body mass
and blood glucose, and decrease with fasting, RYGB, and in post-prandial states following VSG. These changes were mostly opposite to those of acyl-ghrelin. Furthermore, using electrophysiology, we showed that LEAP2 both hyperpolarizes and prevents acyl-ghrelin from activating arcuate NPY neurons. We predict that the plasma LEAP2:acyl-ghrelin molar ratio may be a key determinant modulating acyl-ghrelin
activity in response to body mass, feeding status, and blood glucose
Prolactin
During an oral glucose tolerance test (OGTT) glucose and insulin levels were measured in 26 patients with prolactin-producing pituitary tumours without growth hormone excess. Basal glucose and insulin levels did not differ from the values of an age-matched control group. After glucose load the hyperprolactinaemic patients showed a decrease in glucose tolerance and a hyperinsulinaemia. Bromocriptine (CB 154), which suppressed PRL, improved glucose tolerance and decreased insulin towards normal in a second OGTT. — Human PRL or CB 154 had no significant influence on insulin release due to glucose in the perfused rat pancreas. — These findings suggest a diabetogenic effect of PRL. CB 154 might be a useful drug in improving glucose utilization in hormone-active pituitary tumours
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