Betulinic acid and 1,25(OH)2 vitamin D3 share intracellular signal transduction in glucose homeostasis in soleus muscle

Castro, Allisson Jhonatan Gomes; Frederico, Marisa Jádna Silva; Cazarolli, Luisa Helena; Bretanha, Lizandra C.; Tavares, Luciana de Carvalho; Buss, Ziliani da Silva; Dutra, Márcio Ferreira; Zamoner, Ariane; Pizzolatti, Moacir Geraldo; Silva, Fátima Regina Mena Barreto

doi:10.1016/j.biocel.2013.11.020

Cited by 29 publications

(25 citation statements)

References 51 publications

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“…In agreement with our results, Morus alba root bark extract, which is rich in BA, was effective in reducing blood glucose and lipid peroxidation ( 8 ). In another study, BA increased insulin secretion and muscle glycogen ( 26 ). In one study, BA caused antidiabetic activity by reducing insulin resistance and potentiating β-cell mass and function.…”

Section: Discussionmentioning

confidence: 90%

The effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice

Ahangarpour¹,

Shabani²,

Farbood³

2018

Res Pharma Sci

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Diabetes mellitus is developed by lack of insulin secretion or reduction of tissues sensitivity to insulin, which lead to serious complications. The aim of this study is to evaluate antihyperlipidemic effect of betulinic acid (BA) on streptozotocin-nicotinamide (STZ-NA) induced diabetic mice. In this experimental study, seventy adult male NMRI mice (20-25 g) were divided randomly into seven groups (n = 10) of control, sham, diabetes, diabetes + BA (10, 20 and 40 mg/kg), and diabetes + metformin (200 mg/kg). Diabetes was induced by intraperitoneal (i.p.) injection of a single dose of STZ (50 mg/kg) 15 min after an i.p. administration of nicotinamide (NA) (120 mg/kg). BA and metformin were orally administered and after two weeks blood samples were taken. Blood levels of leptin, adiponectin, lipid profile and liver enzyme were then measured. One day after the last drug administration, liver was removed to evaluate the histological changes. A significant increase (P < 0.05) in the plasma levels of leptin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), alkaline phosphatase (ALP), low density lipoprotein cholesterol (LDL-C), cholesterol, and a significant decrease in adiponectin and high density lipoprotein cholesterol (HDL-C) were observed in diabetic mice. The groups treated with BA indicated a significant decrease in leptin, AST, ALT, ALP, TG, cholesterol, LDL-C and an increases in adiponectin and HDL levels, while VLDL did not show significant changes. BA was found to have positive effects on liver injury. BA has an effective role on liver damage induced by diabetes through amelioration of leptin, adiponectin, liver enzyme levels and lipid profile. Since BA has a positive effect on lipid profile, adiponectin and leptin, it may improve metabolic syndrome.

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Section: Discussionmentioning

confidence: 90%

The effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice

Ahangarpour¹,

Shabani²,

Farbood³

2018

Res Pharma Sci

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“…Calcitriol partially restored VDR, IR, and GLUT4 expression in type 2 diabetic model [92], raising the possibility that vitamin D could contribute to improving insulin signaling in type 2 diabetes mellitus. In a recent study, the effect of 1 α ,25(OH) 2 D 3 on glucose uptake in rat skeletal muscle is investigated [93]. 1 α ,25(OH) 2 D 3 stimulated glucose uptake with increased expression of GLUT4 protein and enhanced translocation of GLUT4 to the plasma membrane not through PI3K-signaling pathway [93], which is essential for insulin-stimulated GLUT4 translocation and glucose transport [94].…”

Section: Vitamin D and Type 2 Diabetes Mellitusmentioning

confidence: 99%

“…In a recent study, the effect of 1 α ,25(OH) 2 D 3 on glucose uptake in rat skeletal muscle is investigated [93]. 1 α ,25(OH) 2 D 3 stimulated glucose uptake with increased expression of GLUT4 protein and enhanced translocation of GLUT4 to the plasma membrane not through PI3K-signaling pathway [93], which is essential for insulin-stimulated GLUT4 translocation and glucose transport [94]. In addition, 1 α ,25(OH) 2 D 3 -stimulated glucose uptake was suppressed concomitantly with downregulation of GLUT4 protein by treatment with cycloheximide [93], suggesting that it may be mediated by genomic signaling of vitamin D. Taken together, vitamin D may improve glucose metabolism in skeletal muscle by modulating GLUT4 expression and translocation through insulin-dependent and/or insulin-independent mechanisms.…”

Section: Vitamin D and Type 2 Diabetes Mellitusmentioning

confidence: 99%

Vitamin D Signaling in Myogenesis: Potential for Treatment of Sarcopenia

Wagatsuma

Sakuma

2014

BioMed Research International

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Muscle mass and strength progressively decrease with age, which results in a condition known as sarcopenia. Sarcopenia would lead to physical disability, poor quality of life, and death. Therefore, much is expected of an effective intervention for sarcopenia. Epidemiologic, clinical, and laboratory evidence suggest an effect of vitamin D on muscle function. However, the precise molecular and cellular mechanisms remain to be elucidated. Recent studies suggest that vitamin D receptor (VDR) might be expressed in muscle fibers and vitamin D signaling via VDR plays a role in the regulation of myoblast proliferation and differentiation. Understanding how vitamin D signaling contributes to myogenesis will provide a valuable insight into an effective nutritional strategy to moderate sarcopenia. Here we will summarize the current knowledge about the effect of vitamin D on skeletal muscle and myogenic cells and discuss the potential for treatment of sarcopenia.

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“…Although the exact mechanisms by which vitamin D influences muscle insulin sensitivity in humans remain to be elucidated, preclinical evidence suggests that vitamin D may improve diabetes-induced muscle dysfunction and atrophy (32) as well as muscle fat infiltration (33). Also, vitamin D could increase glucose uptake in adipose tissue and muscle by stimulating GLUT-4 expression (34,35) and reduce lowgrade chronic systemic inflammation (36,37).…”

Section: Discussionmentioning

confidence: 99%

Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: a randomised, placebo-controlled trial

Lemieux

Weisnagel

Caron

et al. 2019

European Journal of Endocrinology

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Objective To determine whether vitamin D3 supplementation improves insulin sensitivity, using the hyperinsulinemic-euglycemic clamp. Design This single-centre, double-blind, placebo-controlled trial randomised 96 participants at high risk of diabetes or with newly diagnosed type 2 diabetes to vitamin D3 5000 IU daily or placebo for 6 months. Methods We assessed at baseline and 6 months: (1) primary aim: peripheral insulin sensitivity (M-value using a 2-h hyperinsulinemic-euglycemic clamp); (2) secondary aims: other insulin sensitivity (HOMA2%S, Matsuda) and insulin secretion (insulinogenic index, C-peptide area under the curve, HOMA2-B) indices using a 2-h oral glucose tolerance test (OGTT); β-cell function (disposition index: M-value × insulinogenic index); fasting and 2-h glucose post OGTT; HbA1c; anthropometry. Results Baseline characteristics were similar between groups (% or mean ± s.d.): women 38.5%; age 58.7 ± 9.4 years; BMI 32.2 ± 4.1 kg/m2; prediabetes 35.8%; diabetes 20.0%; 25-hydroxyvitamin D (25(OH)D) 51.1 ± 14.2 nmol/L. At 6 months, mean 25(OH)D reached 127.6 ± 26.3 nmol/L and 51.8 ± 16.5 nmol/L in the treatment and placebo groups, respectively (P < 0.001). A beneficial effect of vitamin D3 compared with placebo was observed on M-value (mean change (95% CI): 0.92 (0.24–1.59) vs −0.03 (−0.73 to 0.67); P = 0.009) and disposition index (mean change (95% CI): 267.0 (−343.4 to 877.4) vs −55.5 (−696.3 to 585.3); P = 0.039) after 6 months. No effect was seen on other outcomes. Conclusions In individuals at high risk of diabetes or with newly diagnosed type 2 diabetes, vitamin D supplementation for 6 months significantly increased peripheral insulin sensitivity and β-cell function, suggesting that it may slow metabolic deterioration in this population.

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Betulinic acid and 1,25(OH)2 vitamin D3 share intracellular signal transduction in glucose homeostasis in soleus muscle

Cited by 29 publications

References 51 publications

The effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice

The effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice

Vitamin D Signaling in Myogenesis: Potential for Treatment of Sarcopenia

Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: a randomised, placebo-controlled trial

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