Glucose-stimulated insulin secretion depends on FFA1 and Gq in neonatal mouse islets

• DOI: 10.1007/s00125-023-05932-5
• Publication Date: 2023-05-23T01:03:36Z
• Authors: Estela Lorza-Gil; Gabriele Kaiser; Christopher Carlein; Markus D. A. Hoff...; Gabriele M. König; Sieglinde Haug; Leticia Prates Roma; Elisabeth Rexen U...; Trond Ulven; Evi Kostenis; Andreas L. Birken...; Hans-Ulrich Häring; Susanne Ullrich; Felicia Gerst
• Keywords: NEFA; Pancreatic Islets; Tolbutamide; Insulin oscillation

Abstract Aims/hypothesis After birth, the neonatal islets gradually acquire glucose-responsive insulin secretion, a process that is subjected to maternal imprinting. Although NEFA are major components of breastmilk and secretagogues, their role for functional maturation beta cells still unclear. endogenous ligands fatty acid receptor 1 (FFA1, encoded by Ffar1 in mice), Gq-coupled with stimulatory effect on secretion. This study investigates FFA1 cell function adaptation offspring parental high-fat feeding. Methods Wild-type (WT) −/− mice were fed (HFD) or chow diet (CD) 8 weeks before mating, during gestation lactation. Blood variables, pancreas weight content assessed 1-, 6-, 11- 26-day old (P1–P26) offspring. Beta mass proliferation determined P1–P26 pancreatic tissue sections. FFA1/Gq dependence secretion was evaluated isolated INS-1E using pharmacological inhibitors siRNA strategy. Transcriptome analysis conducted islets. Results glucose levels higher CD-fed P6-offspring compared WT P6-offspring. Accordingly, glucose-stimulated (GSIS) its potentiation palmitate impaired CD P6-islets. In P6-islets, stimulated four- fivefold five- sixfold over GSIS exendin-4, respectively. HFD increased blood P6-offspring, it did not change from contrast, abolished responsiveness (i.e. GSIS) Inhibition Gq FR900359 YM-254890 P6-islets mimicked deletion, i.e. suppression palmitate-augmented GSIS. The blockage Gi/o pertussis toxin (PTX) enhanced (100-fold) rendered responsive, suggesting constitutive activation Gi/o. cancelled 90% PTX-mediated stimulation, while completely PTX-elevated secretory defect originate insufficient cells, since offspring’s age irrespective genotype diet. spite that, breastfed P1–P11) had genotype- diet-driven dynamic. Under CD, highest rate reached P6 (3.95% vs 1.88% P6), whose also showed mRNA genes (e.g. Fos , Egr1 Jun ) typically high immature cells. both (4.48%) (5.19%) P11 offspring, only significantly upon (5.18 µg under 16.93 HFD). Conclusions/interpretation promotes newborn required adaptive face metabolic challenge, such as HFD. Graphical