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Glucagon increased satiety in some patients with type 1 diabetes
New data demonstrate glucagon significantly increased feelings of satiety among healthy lean participants and in patients with type 1 diabetes, but not among those who were obese.
“Once a person becomes obese, glucagon no longer induces feelings of fullness,” Ayman M. Arafat, MD, of Charité-University Medicine in Berlin, Germany, said in a press release. “Further research is needed to determine why glucagon no longer suppresses appetite effectively in this population, even though they are otherwise healthy.”
Ayman M. Arafat
Patients considered “healthy obese” (n=11), those with type 1 diabetes (n=13) and those considered to be lean (n=13) underwent measurements of: fasting baseline levels of adrenocorticotropic hormone (ACTH), cortisol, TSH, free thyroxine, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol and sex hormone-binding globulin (SHBG); as well as insulin tolerance tests and/or growth hormone stimulation tests.
Glucagon significantly increased the satiety index among patients with type 1 diabetes and those considered to be lean (P<.001), according to results from the prospective, double-blind, placebo-controlled study. However, glucagon did not induce satiety in healthy obese patients (P=.152), researchers added.
Data also indicate total-ghrelin significantly dropped following the administration of glucagon among all three study groups (P<.01). According to researchers, measurements of acyl-ghrelin also fell among lean participants (P<.01), but showed no significant decreases among the healthy obese cohort (P=.248). Further, acyl-ghrelin tended to increase in patients with type 1 diabetes (P<.01), researchers wrote.
These changes in acyl-ghrelin after the administration of glucagon were linked to changes in concentrations of nonesterified fatty acids in all groups at 30 minutes (P<.001), 60 minutes (P<.01) and 120 minutes (P<.05), according to researchers.
“The findings could influence efforts to develop new treatments for obesity and diabetes,” Arafat said. “Although therapeutic agents that influence glucagon and other hormones currently are considered a promising avenue for research, this study suggests a treatment involving glucagon may be ineffective in controlling meal size in people who are obese.”
Disclosure: The researchers report no relevant financial disclosures.
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The success of bariatric surgery has challenged research into the mechanism of why it works to alter body set point through appetite and satiety regulation. This research has propelled the gut as an endocrine organ into the limelight along with the hormones it secretes: ghrelin, PYY, GLP-1 and GIP among others. The gut is now known as one of the dominant regulators of energy balance.
Glucagon has been largely known in the past as the antidote of insulin, at least for its effects on blood glucose. Insulin also has powerful effects on appetite suppression and the role of glucagon in appetite and satiety is being investigated as well.
The paper by Arafat and colleagues documents the administration of glucagon to human subjects and measured effects on lean, obese persons and those with type 1 diabetes with outcome measures being satiety, acyl-ghrelin and total ghrelin levels.
Ghrelin is a peptide that induces appetite and acyl ghrelin is considered to be the active form for this orexigenic effect.
Results from this study confirm that glucagon suppresses total ghrelin levels and this is preserved in obesity and type 1 diabetes, suggesting independence from insulin levels. The effect of glucagon on satiety was preserved in type 1 diabetes but lost in obesity. Interestingly, glucagon does not decrease acyl-ghrelin concentrations in type 1 diabetes and obesity but does in lean persons.
Dietary medium chain fatty acids are the principle source of acylation of ghrelin. Preservation of glucose induced suppression of acyl-ghrelin only occurs in leans and this study showed an increase in acyl-ghrelin along with NEFA (surrogate marker of lipolysis) after glucagon administration in type 1 diabetes. In obesity, acyl-ghrelin levels after glucagon administration are unchanged. The authors postulate that the enhancement of ghrelin acylation many be related to the modification of lipolysis by the glucagon-insulin interaction. This intriguing concept needs further study.
This study demonstrates that glucagon administration fails to decrease hunger is obese subjects but does so in type 1 diabetes and in lean persons. This suggests a resistance to glucagon-induced satiety in obesity, work that needs corroboration and further study.
This work on glucagon administration and satiety in leans, obese and type 1 diabetes confirms the added complexity of appetite and satiety regulation with this research on glucagon. This study contributes to the continuation of work on glucagon and its role in the gut–hypothalamus and pituitary axis.
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