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Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11.

ABSTRACT: In mammals, blood glucose levels likely play a role in appetite regulation yet the mechanisms underlying this phenomenon remain opaque. Mechanisms can often be explored from Drosophila genetic approaches. To determine if circulating sugars might be involved in Drosophila feeding behaviors, we scored hemolymph glucose and trehalose, and food ingestion in larvae subjected to various diets, genetic mutations, or RNAi. We found that larvae with glucose elevations, hyperglycemia, have an aversion to feeding; however, trehalose levels do not track with feeding behavior. We further discovered that insulins and SLC5A11 may participate in glucose-regulated feeding. To see if food aversion might be an appropriate screening method for hyperglycemia candidates, we developed a food aversion screen to score larvae with abnormal feeding for glucose. We found that many feeding defective larvae have glucose elevations. These findings highlight intriguing roles for glucose in fly biology as a potential cue and regulator of appetite.

SUBMITTER: Ugrankar R

PROVIDER: S-EPMC6123810 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11.

Ugrankar Rupali R Theodoropoulos Pano P Akdemir Fatih F Henne W Mike WM Graff Jonathan M JM

Communications biology 20180813

In mammals, blood glucose levels likely play a role in appetite regulation yet the mechanisms underlying this phenomenon remain opaque. Mechanisms can often be explored from Drosophila genetic approaches. To determine if circulating sugars might be involved in Drosophila feeding behaviors, we scored hemolymph glucose and trehalose, and food ingestion in larvae subjected to various diets, genetic mutations, or RNAi. We found that larvae with glucose elevations, hyperglycemia, have a ...[more]

PMID: 30271990

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Project description:Little is known about the molecular underpinning of behavioral pleiotropy. The Drosophila melanogaster foraging gene is highly pleiotropic, affecting many independent larval and adult phenotypes. Included in foraging's multiple phenotypes are larval foraging path length, triglyceride levels, and food intake. foraging has a complex structure with four promoters and 21 transcripts that encode nine protein isoforms of a cGMP dependent protein kinase (PKG). We examined if foraging's complex molecular structure underlies the behavioral pleiotropy associated with this gene. Using a promotor analysis strategy, we cloned DNA fragments upstream of each of foraging's transcription start sites and generated four separate forpr-Gal4s. Supporting our hypothesis of modular function, they had discrete, restricted expression patterns throughout the larva. In the CNS, forpr1-Gal4 and forpr4-Gal4 were expressed in neurons while forpr2-Gal4 and forpr3-Gal4 were expressed in glia cells. In the gastric system, forpr1-Gal4 and forpr3-Gal4 were expressed in enteroendocrine cells of the midgut while forpr2-Gal4 was expressed in the stem cells of the midgut. forpr3-Gal4 was expressed in the midgut enterocytes, and midgut and hindgut visceral muscle. forpr4-Gal4's gastric system expression was restricted to the hindgut. We also found promoter specific expression in the larval fat body, salivary glands, and body muscle. The modularity of foraging's molecular structure was also apparent in the phenotypic rescues. We rescued larval path length, triglyceride levels (bordered on significance), and food intake of for0 null larvae using different forpr-Gal4s to drive UAS-forcDNA. In a foraging null genetic background, forpr1-Gal4 was the only promoter driven Gal4 to rescue larval path length, forpr3-Gal4 altered triglyceride levels, and forpr4-Gal4 rescued food intake. Our results refine the spatial expression responsible for foraging's associated phenotypes, as well as the sub-regions of the locus responsible for their expression. foraging's pleiotropy arises at least in part from the individual contributions of its four promoters.

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Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11.

Publications

Circulating glucose levels inversely correlate with <i>Drosophila</i> larval feeding through insulin signaling and SLC5A11.

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