| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Wiemerslage, Lyle, et al.
(författare)
-
The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling
- 2016
-
Ingår i: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 229:3, s. 233-243
-
Tidskriftsartikel (refereegranskat)abstract
- Transmembrane protein 18 (TMEM18) is an ill-described, obesity-related gene, but few studies have explored its molecular function. We found single-nucleotide polymorphism data, suggesting that TMEM18 may be involved in the regulation/physiology of metabolic syndrome based on associations with insulin, homeostatic model assessment-beta (HOMA beta), triglycerides, and blood sugar. We then found an ortholog in the Drosophila genome, knocked down Drosophila Tmem18 specifically in insulin-producing cells, and tested for its effects on metabolic function. Our results suggest that TMEM18 affects substrate levels through insulin and glucagon signaling, and its downregulation induces a metabolic state resembling type 2 diabetes. This work is the first to experimentally describe the metabolic consequences of TMEM18 knockdown, and further supports its association with obesity.
|
|
| 6. |
- Williams, Michael J., et al.
(författare)
-
Dibutyl Phthalate Exposure Disrupts Evolutionarily Conserved Insulin and Glucagon-Like Signaling in Drosophila Males
- 2016
-
Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 157:6, s. 2309-2321
-
Tidskriftsartikel (refereegranskat)abstract
- Phthalate diesters are commonly used as industrial plasticisers, as well as in cosmetics and skin care products, as a result people are constantly exposed to these xenobiotics. Recent epidemiological studies have found a correlation between circulating phthalate levels and type 2 diabetes, whereas animal studies indicate that phthalates are capable of disrupting endocrine signaling. Nonetheless, how phthalates interfere with metabolic function is still unclear. Here, we show that feeding Drosophila males the xenobiotic dibutyl phthalate (DBP) affects conserved insulin- and glucagon-like signaling. We report that raising flies on food containing DBP leads to starvation resistance, increased lipid storage, hyperglycemia, and hyperphagia. We go on to show that the starvation-resistance phenotype can be rescued by overexpression of the glucagon analogue adipokinetic hormone (Akh). Furthermore, although acute DBP exposure in adult flies is able to affect insulin levels, only chronic feeding influences Akh expression. We establish that raising flies on DBP-containing food or feeding adults DBP food affects the expression of homologous genes involved in xenobiotic and lipid metabolism (AHR [Drosophila ss], NR1I2 [Hr96], ABCB1 [MDR50], ABCC3 [MRP], and CYP3A4 [Cyp9f2]). Finally, we determined that the expression of these genes is also influenced by Akh. Our results provide comprehensive evidence that DBP can disrupt metabolism in Drosophila males, by regulating genes involved in glucose, lipid, and xenobiotic metabolism.
|
|
