The Glucagon-Like Adipokinetic Hormone in Drosophila melanogaster – Biosynthesis and Secretion

Abstract

Metabolic homeostasis requires the precise regulation of circulating sugar titers. In mammals, homeostatic control of circulating sugar titers requires the coordinated secretion and systemic activities of glucagon and insulin. Metabolic homeostasis is similarly regulated in Drosophila melanogaster through the glucagon-like adipokinetic hormone (AKH) and the Drosophila insulin-like peptides (DILPs). In flies and mammals, glucagon and AKH are biosynthesized in and secreted from specialized endocrine cells. KATP channels borne on these cells respond to fluctuations in circulating glucose titers and thereby regulate glucagon secretion. The influence of glucagon in the pathogenesis of type 2 diabetes mellitus is now recognized, and a crucial mechanism that regulates glucagon secretion was reported nearly a decade ago. Ongoing efforts to develop D. melanogaster models for metabolic syndrome must build upon this seminal work. These efforts make a critical review of AKH physiology timely. This review focuses on AKH biosynthesis and the regulation of glucose-responsive AKH secretion through changes in CC cell electrical activity. Future directions for AKH research in flies are discussed, including the development of models for hyperglucagonemia and epigenetic inheritance of acquired metabolic traits. Many avenues of AKH physiology remain to be explored and thus present great potential for improving the utility of D. melanogaster in metabolic research.

Diet supplementation with egg yolk powder fattens the beetle Tribolium castaneum

“…On the other hand, HFD increases levels of the AKH receptor (R. Huang et al, 2020), a hormone involved in mobilizing energy reserves in the fat body and maintaining glucose levels in the hemolymph (Hughson, 2021). F I G U R E 5 Diet supplementation with egg yolk powder does not alter the expression profile of metabolic genes.…”

“…On the other hand, HFD increases levels of the AKH receptor (R. Huang et al, 2020), a hormone involved in mobilizing energy reserves in the fat body and maintaining glucose levels in the hemolymph (Hughson, 2021). Furthermore, this treatment also alters the expression of ILPs (Birse et al, 2010; de Paula et al, 2018; Liao et al, 2021; Nayak & Mishra, 2021), which are involved in the regulation of metabolism and development, and their increased expression is a diabetic phenotype typically seen in hypercaloric diet treatments in insects (Chowański et al, 2021).…”

Mechanisms of Neuroendocrine Stress Response in Drosophila and Its Effect on Carbohydrate and Lipid Metabolism

“…In D. melanogaster , IPCs are similar to vertebrate pancreatic β-cells secreting insulin in response to hyperglycemia, and the role of pancreatic α-cells secreting glucagon in response to hypoglycemia is performed by the cells of the corpus cardiacum ( CC ) gland, which produce a glucagon-like neuropeptide, the adipokinetic hormone (AKH) [ 3 , 29 , 30 , 31 ]. Due to the similarity of their functions to those of α- and β-cells, IPCs and CC , taken together, are seen as the Drosophila analogue of the mammalian pancreatic gland [ 32 ].…”

Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions

“…The Drosophila hormones AKH and DILPs display functions analogous to mammalian glucagon and insulin/insulin-like growth factors, respectively [ 174 , 217 – 221 ]. Although these hormones are commonly associated with regulation of metabolism in adult flies, they also affect nutrient-dependent behaviours (see [ 93 , 222 – 228 ]).…”

“…Instead, we briefly summarize some regulatory mechanisms that orchestrate behaviour in flies by means of hormonal signalling. The Drosophila hormones AKH and DILPs display functions analogous to mammalian glucagon and insulin/ insulin-like growth factors, respectively [174,[217][218][219][220][221]. Although these hormones are commonly associated with regulation of metabolism in adult flies, they also affect nutrient-dependent behaviours (see [93,[222][223][224][225][226][227][228]).…”