Gluconeogenic Enzymes in β-Cells: Pharmacological Targets for Improving Insulin Secretion

Westermeier, Francisco; Holyoak, Todd; Asenjo, Joel L.; Gatica, Rodrigo; Nualart, Francisco; Burbulis, Ian; Bertinat, Romina

doi:10.1016/j.tem.2019.05.004

Cited by 10 publications

(6 citation statements)

References 90 publications

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“…Elvert et al reported that alterations in body weight during antihyperglycaemic treatment are closely related to the mechanism of action by which the drug controls blood glucose (Elvert et al, 2013). Pancreatic ß-cells express the gluconeogenic enzymes glucose 6-phosphatase (G6Pase), which modulate glucose-stimulated insulin secretion through their ability to reverse otherwise irreversible glycolytic steps (Westermeier et al, 2019). In this present study, WVBF intervention significantly improved body weight and insulin secretion in diabetic rats.…”

Section: Discussionmentioning

confidence: 48%

Veratrilla baillonii Franch Ameliorates Diabetic Liver Injury by Alleviating Insulin Resistance in Rats

Zhang

et al. 2021

Front. Pharmacol.

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Type 2 diabetes mellitus (T2DM) is a complex and polygenic disorder with diverse complications. Veratrilla baillonii Franch (V. baillonii) has been applied in the intervention and treatment a diverse range of diseases, including diabetes. In this study, we revealed that water extracts of V. baillonii (WVBF) can ameliorate liver injury and insulin resistance in T2DM rat model. To elucidate the anti-diabetic mechanisms of WVBF, we performed liver transcriptome analysis that displayed WVBF treatment significantly suppressed many gene expressions involved in insulin resistance. Furthermore, functional experiments showed that WVBF treatment reduced the pathological damages of liver and pancreas, which may be regulated by Foxo1, Sirt1, G6pc, c-Met, Irs1, Akt1, Pik3r1. These results indicated that WVBF improves diabetic liver injury and insulin resistance in diabetic rats. Therefore, this study demonstrated WVBF could be used as a promising therapeutic agent for intervention and treatment of diabetes.

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Section: Discussionmentioning

confidence: 48%

Veratrilla baillonii Franch Ameliorates Diabetic Liver Injury by Alleviating Insulin Resistance in Rats

Zhang

et al. 2021

Front. Pharmacol.

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“…The transcription of rate-limiting enzyme genes, such as those of PCK and FBP , is an important step toward activating hepatic gluconeogenesis ( Westermeier et al., 2019 ), particularly in cattle. To determine the differences in the expression of PCK and FBP in cattle and non-ruminant animals, we analysed the liver transcriptome data of pigs/humans and cattle, and found that the cattle liver can powerfully stimulate the expression of PCK as well as FBP ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The liver plays a major role in maintaining glucose homeostasis in mammals. Although many steps of gluconeogenesis are the reverse reaction of glycolysis, the respective rate-limiting steps catalyzed by G6PC, FBP, and PCK reverse the glycolysis and promote gluconeogenesis ( Lebigot et al., 2015 ; Westermeier et al., 2019 ). Yet, the distinguishing physiological characteristic of cattle is their high-efficiency hepatic gluconeogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…These characteristics determined that more hepatic gluconeogenesis processes occurred in cattle than in non-ruminants, which may be induced by the higher efficiency of gluconeogenesis in cattle. Many steps of gluconeogenesis are the reverse reaction of glycolysis, wherein the respective rate-limiting steps catalysing glucose 6-phosphatase (G6PC), fructose 1,6-bisphosphatase (FBP), and phosphoenolpyruvate carboxykinase (PCK) reverse the glycolysis and promote gluconeogenesis ( Westermeier et al., 2019 ). The expression of genes encoding G6PC, FBP, and PCK is a prerequisite for hepatic gluconeogenesis, thus playing a major role in endogenous glucose production to maintain lactose synthesis and milk production in cattle.…”

Section: Introductionmentioning

confidence: 99%

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The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α

Wang

Zhang²,

Wu³

et al. 2022

Animal Nutrition

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“…In the past decade, inhibitor of dipeptylpeptidase 4 (iDPP4) and sodiumglucose cotransporter-2 (SGLT-2) have been included in T2DM treatments, either monotherapy or in combination therapy, and currently represent the leading T2DM therapies [14][15][16]. However, these therapies do not prevent disease progression in most cases, and long-term administration can lead to drug tolerance and systemic toxicity [17][18][19]. The lack of T2DM treatment effectiveness can be explained by the nonspecific mechanism of action in the current therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from Californiconus californicus, for Treating Type 2 Diabetes

et al. 2021

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The FDA’s approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from Conus species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membrane receptors, or ligands alter normal physiological functions, as in metabolic diseases such as Type 2 diabetes. In this study, the synthetic cal14.2b (s-cal14.2b) from the unusual Californiconus californicus demonstrated bioactivity on NIT-1 insulinoma cell lines stimulating insulin secretion detecting by high performance liquid chromatography (HPLC). Accordingly, s-cal14.2b increased the CaV1.2/1.3 channel-current by 35 ± 4% with a recovery τ of 10.3 ± 4 s in primary cell culture of rat pancreatic β-cells. The in vivo results indicated a similar effect of insulin secretion on mice in the glucose tolerance curve model by reducing the glucose from 500 mg/dL to 106 mg/dL in 60 min, compared to the negative control of 325 mg/dL at the same time. The PET-SCAN with radiolabeling 99mTc-s-cal14.2b demonstrated biodistribution and accumulation in rat pancreas with complete depuration in 24 h. These findings show the potential therapeutic use of s-cal14.2b in endocrinal pathologies such as early stages of Type 2 Diabetes where the pancreas’s capability to produce insulin is still effective.

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Gluconeogenic Enzymes in β-Cells: Pharmacological Targets for Improving Insulin Secretion

Cited by 10 publications

References 90 publications

Veratrilla baillonii Franch Ameliorates Diabetic Liver Injury by Alleviating Insulin Resistance in Rats

Veratrilla baillonii Franch Ameliorates Diabetic Liver Injury by Alleviating Insulin Resistance in Rats

The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α

Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from Californiconus californicus, for Treating Type 2 Diabetes

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