Free fatty acid receptors in the endocrine regulation of glucose metabolism: Insight from gastrointestinal-pancreatic-adipose interactions

Zhao, Yufeng

doi:10.3389/fendo.2022.956277

Cited by 7 publications

(6 citation statements)

References 155 publications

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“…KEGG pathways analysis (Figure 4) also revealed many genes contributing to fat digestion and absorption pathways. Free fatty acids (FFAs) in particular have complex actions in the pancreas, but nevertheless are important regulators in glucose metabolism and insulin release, and the activation of their receptors directly impacts pancreas secretion [27]. They can also stimulate the release of CCK from enteroendocrine cells, which in turn induces pancreatic enzyme secretion.…”

Section: Discussionmentioning

confidence: 99%

“…They can also stimulate the release of CCK from enteroendocrine cells, which in turn induces pancreatic enzyme secretion. While short-term exposure to FFAs, specifically long-chain fatty acids, results in insulin release from β-cells, it has been well documented that chronic exposure and/or lipotoxicity results in desensitization, impaired GSIS, insulin resistance, and, over the long-term, β-cell damage [27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

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Fetal Hypoglycemia Induced by Placental SLC2A3-RNA Interference Alters Fetal Pancreas Development and Transcriptome at Mid-Gestation

Kennedy,

Lynch,

Tanner

et al. 2024

IJMS

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Glucose, the primary energy substrate for fetal oxidative processes and growth, is transferred from maternal to fetal circulation down a concentration gradient by placental facilitative glucose transporters. In sheep, SLC2A1 and SLC2A3 are the primary transporters available in the placental epithelium, with SLC2A3 located on the maternal-facing apical trophoblast membrane and SLC2A1 located on the fetal-facing basolateral trophoblast membrane. We have previously reported that impaired placental SLC2A3 glucose transport resulted in smaller, hypoglycemic fetuses with reduced umbilical artery insulin and glucagon concentrations, in addition to diminished pancreas weights. These findings led us to subject RNA derived from SLC2A3-RNAi (RNA interference) and NTS-RNAi (non-targeting sequence) fetal pancreases to qPCR followed by transcriptomic analysis. We identified a total of 771 differentially expressed genes (DEGs). Upregulated pathways were associated with fat digestion and absorption, particularly fatty acid transport, lipid metabolism, and cholesterol biosynthesis, suggesting a potential switch in energetic substrates due to hypoglycemia. Pathways related to molecular transport and cell signaling in addition to pathways influencing growth and metabolism of the developing pancreas were also impacted. A few genes directly related to gluconeogenesis were also differentially expressed. Our results suggest that fetal hypoglycemia during the first half of gestation impacts fetal pancreas development and function that is not limited to β cell activity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fetal Hypoglycemia Induced by Placental SLC2A3-RNA Interference Alters Fetal Pancreas Development and Transcriptome at Mid-Gestation

Kennedy,

Lynch,

Tanner

et al. 2024

IJMS

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“…73 Under low glucose concentrations, FFAs are converted to long-chain fatty acid coenzyme A (LC-CoA) by long-chain acyl-CoA synthetase and enter the mitochondria where they undergo β-oxidation to generate energy, 74 thus, the hypoglycemia is prevented. 75–77 However, in one study it has been demonstrated that FFA induced insulin secretion independent on the oxidation of the fuel 78 and/or presence of glucose. 76 In contrast, excess consumption of dietary fats and oils has a negative impact on β-cells.…”

Section: Risk Factors For β-Cell Dysfunction In Type 2 Diabetesmentioning

confidence: 99%

Pancreatic Beta-cell Dysfunction in Type 2 Diabetes

Khin

Lee

2023

Eur J Inflamm

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Pancreatic β-cells produce and secrete insulin to maintain blood glucose levels within a narrow range. Defects in the function and mass of β-cells play a significant role in the development and progression of diabetes. Increased β-cell deficiency and β-cell apoptosis are observed in the pancreatic islets of patients with type 2 diabetes. At an early stage, β-cells adapt to insulin resistance, and their insulin secretion increases, but they eventually become exhausted, and the β-cell mass decreases. Various causal factors, such as high glucose, free fatty acids, inflammatory cytokines, and islet amyloid polypeptides, contribute to the impairment of β-cell function. Therefore, the maintenance of β-cell function is a logical approach for the treatment and prevention of diabetes. In this review, we provide an overview of the role of these risk factors in pancreatic β-cell loss and the associated mechanisms. A better understanding of the molecular mechanisms underlying pancreatic β-cell loss will provide an opportunity to identify novel therapeutic targets for type 2 diabetes.

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“…Ingestible fats consist mainly of long-chain triglycerides (LCTs); overaccumulation of LCTs leads to hepatic steatosis and insulin resistance, both of which are closely linked to cardiovascular disease, cancer, and death (3)(4)(5). To prevent the onset and exacerbation of such lifestyle-related diseases, receptors and hormones involved in digestion, absorption, and accumulation of LCTs have drawn much attention recently (6,7).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-fat diet feeding

Yasuda

Harada

Hatoko

et al. 2023

American Journal of Physiology-Endocrinology and Metabolism

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G-protein-coupled receptor (GPR) 120 is expressed in enteroendocrine cells secreting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP), and cholecystokinin (CCK). Although GPR120 signaling in adipose tissue and macrophages has been reported to ameliorate obesity and insulin resistance on high long-chain triglyceride (LCT) diet, intestine-specific roles of GPR120 are unclear. To clarify the metabolic effect of GPR120 in intestine, we generated intestine-specific GPR120-knockout (GPR120int-/-) mice. In comparison with floxed GPR120 (WT) mice, GPR120int-/- mice exhibited reduced GIP secretion and CCK action without change of insulin, GLP-1, or peptide YY (PYY) secretion after single administration of LCT. Under a high-LCT diet, GPR120int-/- mice showed mild reduction of body weight and substantial amelioration of insulin resistance and fatty liver. Moreover, liver and white adipose tissue (WAT) of GPR120int-/- mice exhibited increased Akt phosphorylation and reduced gene expression of suppressor of cytokine signaling (SOCS) 3, which inhibits insulin signaling. In addition, gene expression of inflammatory cytokines in WAT and lipogenic molecules in liver were reduced in GPR120int-/- mice. These findings suggest that inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-LCT diet feeding.

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Free fatty acid receptors in the endocrine regulation of glucose metabolism: Insight from gastrointestinal-pancreatic-adipose interactions

Cited by 7 publications

References 155 publications

Fetal Hypoglycemia Induced by Placental SLC2A3-RNA Interference Alters Fetal Pancreas Development and Transcriptome at Mid-Gestation

Fetal Hypoglycemia Induced by Placental SLC2A3-RNA Interference Alters Fetal Pancreas Development and Transcriptome at Mid-Gestation

Pancreatic Beta-cell Dysfunction in Type 2 Diabetes

Inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-fat diet feeding

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