PRACA PRZEGLĄDOWA
Rola suplementacji w insulinooporności
Więcej
Ukryj
1
Katedra Biotechnologii, Mikrobiologii i Żywienia Człowieka, Wydział Nauk o Żywności i Biotechnologii, Uniwersytet Przyrodniczy w Lublinie, Polska
Autor do korespondencji
Paweł Glibowski
Katedra Biotechnologii, Mikrobiologii i Żywienia Człowieka
Wydział Nauk o Żywności i Biotechnologii
Uniwersytet Przyrodniczy w Lublinie, Skromna 8, 21-704, Lublin, Polska
Med Og Nauk Zdr. 2023;29(3):153-165
SŁOWA KLUCZOWE
DZIEDZINY
STRESZCZENIE
Wprowadzenie i cel:
Celem przeglądu było przedstawienie wpływu suplementów diety na poprawę wskaźników laboratoryjnych w insulinooporności. Opisano mechanizm działania takich związków jak antocyjany, kurkumina, berberyna, witamina B12.
Metody przeglądu:
Przeprowadzono przegląd literatury na temat suplementacji w insulinooporności, obejmujący prace pełnotekstowe indeksowane w bazie PubMed. Elektroniczne wyszukiwanie literatury przeprowadzono z ograniczeniem do konkretnych lat publikacji (2007–2022), przy użyciu terminów wyszukiwania w postaci następujących słów kluczowych: „insulinooporność”, „cukrzyca”, „berberyna”, „antocyjany”, „kwasy tłuszczowe”, „kurkumina”, „witamina B12”, „Policaptil Gel Retard”. Analizie poddano wszystkie wyszukane artykuły i włączono do przeglądu zarówno prace oryginalne, jak i badania randomizowane podwójnie zaślepione, kontrolowane placebo.
Opis stanu wiedzy:
Dostępne dane wykazują, że na IR (ang. insulin resistance – insulinooporność) wpływa wiele różnych czynników, takich jak czynniki genetyczne, wiek czy też otyłość. Najważniejszym aspektem jest natomiast styl życia. Leczenie insulinooporności polega zatem na zmianie diety oraz zwiększeniu aktywności fizycznej. Niektóre badania udowadniają, że połączenie takiego postępowania z trafnie dobranymi suplementami diety może okazać się bardzo korzystne. Zawarte w nich związki, takie jak antyoksydanty, wykazują działanie przeciwutleniające i przeciwzapalne. Wiele cennych badań potwierdza silne działanie hipolipidemiczne, hipoglikemiczne niektórych roślin oraz takie, których efektem jest uwrażliwienie komórek na insulinę.
Podsumowanie:
Obecnie istnieje coraz więcej dowodów potwierdzających skuteczność stosowania suplementów roślinnych w insulinooporności. W pracy opisano wpływ niektórych składników i roślin na poprawę metabolizmu glukozy i wrażliwości na insulinę.
Introduction and objective:
The aim of the review was to characterise the effects of dietary supplements on the improvement of laboratory indicators in insulin resistance. The mechanism of action of such compounds as e.g. anthocyanins, curcumin, berberine, vitamin B12 is described.
Review methods:
A literature review on supplementation in insulin resistance was conducted, including full-text articles indexed in the PubMed database. An electronic literature search was conducted, restricted to specific years of publication (2007–2022), using search terms in the form of the following key words: ‘insulin resistance’, ‘diabetes’, ‘berberine’, ‘anthocyanins’, ‘fatty acids’, ‘curcumin’, ‘vitamin B12’, and ‘Policaptil Gel Retard’. All retrieved articles were analysed and both original articles and randomised double-blind, placebo-controlled studies were included in the review.
Abbreviated description of the state of knowledge:
Available data show that IR (Insulin Resistance) is affected by many different factors, such as genetics, age, or obesity. However, the most important aspect is life style. Therefore, treatment consists of changing the diet and increasing physical activity. Some studies report that a combination of such a procedure with carefully selected dietary supplements may prove highly beneficial. The compounds they contain, such as antioxidants, have a free radical scavenging effect and exhibit anti-inflammatory properties. Many valuable studies confirm an impressive role of certain plants in their hypolipidemic, hypoglycaemic and insulin-sensitising actions.
Summary:
Currently, there is an inceasing evidence confirming the effectiveness of using plant supplements in insulin resistance. The article describes the mechanism of action of some ingredients and plants to improve glucose metabolism and insulin sensitivity.
SKRÓTY
(PI3K)/Akt – szlak fosfatydyloinozytolu 3-kinazy
GLUT4 – transporter glukozy
AMPK – monofosforan adenozyny
AMP – adenozyno-5’-monofosforan-adenosine monophosphate
MAPK – mitogen-activated protein kinase – kinaza białkowa aktywowana mitogenem
AMPK/ACC – 5’AMP-activated protein kinase/acetyl-CoA carboxylase
PPAR-γ – receptory aktywowane przez proliferatory peroksysomów
HOMA-IR – homeostatic model assessment of insulin resistance – homeostatyczna ocena insulinooporności
LDL – lipoproteina o niskiej gęstości
PGC-1α – PPAR-γ koaktywator 1α – koaktywator 1 alfa receptora aktywowanego proliferatorami peroksysomów
T2DM – cukrzyca typu 2
STZ – streptozotocyna
IL-6 – interleukina 6
TNF-α – czynnik martwicy nowotworów-α
MCP-1 – białko chemotaktyczne monocytów 1
NF-kB – czynnik jądrowego-κB
MCP-1 – monocyte chemoattractant protein-1
IL-1β – interleukina 1
IL-6 – interleukina 6
COX2 – cyklooksygenaza 2
HbA1c – hemoglobina glikowana
PCOS – zespół policystycznych jajników
PI3K/Akt/mTOR – PI3K-phosphoinositide 3 kinase/Akt/mechanistic target of rapamycin-mTOR
NF-kB – czynnik jądrowy kappa-light-chain-enhancer of activated B cells
LDLR – receptor lipoprotein o niskiej gęstości
SIRT1 – silent information regulator 1 – czynnik genetyczny prowadzący do spadku funkcji receptora androgenowego
PGC-1α – peroxisome proliferator-activated receptor gamma coactivator 1-alpha – koaktywator 1-alfa receptora aktywowanego przez proliferatory peroksysomów
MS – zespół metaboliczny
SM – sclerosis multiplex – stwardnienie rozsiane
FPG – stężenie glukozy w osoczu na czczo
TLR-4 – toll-like receptor-4
IL-8 – interleukina 8
5-LOX – lipooksygenaza
BBR – berberyna
PKC – protein kinase C – kinaza białkowa C
InsR – insulin receptor – receptor insulinowy
CRP – białko C-reaktywne
iNOS – indukowalna syntazy tlenku azotu
CCR2 – receptor chemokiny (motyw C-C) 2
MMP-9 – metaloproteaza macierzy 9
LPS – lipopolisacharyd
TLR4/MyD88/NFκB – toll-like receptor 4/mieloidalny czynnik różnicowania 88/czynnik jądrowy-κB
Nrf2 – czynnik jądrowy związany z erytroidami-2
GLUT4 – transporter glukozy typu 4
ERK – extracellular-signal regulated kinase
JNK – kinaza c-Jun N-terminalna
AP-1 – białko aktywatora 1
GDM – Gestational Diabetes Mellitus
IR – insulin resistance – insulinooporność
IKKβ – inhibitor kinazy kappa β
PEPCK – karboksykinaza fosfoenolopirogronianowa
G6Pase – glukozo-6-fosfataza
LKB1 – kinaza wątrobowa B1
TORC2 – koaktywator transkrypcji 2
cAMP – 3’,5’-cyclic adenosine monophosphate – cykliczny adenozyno-3’,5’-monofosforan
CREB – cAMP response element-binding protein
Leukotriene B4 (LTB 4) receptor 1 (BLT1)
BLT1 – leukotriene B4 receptor 1
HNF-4α – hepatic nuclear factor 4α – wątrobowy czynnik jądrowy 4 alfa
IRS2 – substrat receptora insulinowego 2
GLP-1 – glucagon-like peptide-1 – glukagonopodobny peptyd-1
polisacharydami, pochodzących z traganka błoniastego (Astragalus membranaceus) – AP
SCFA – krótkołańcuchowe kwasy tłuszczowe
BCAA – aminokwasy rozgałęzione
AAA – aromatic amino acids – aminokwasy aromatyczne
AUC – area under the curve – pole pod krzywą
TG – triglicerydy
TC – cholesterol całkowity
LDL-C – low density lipoproteins
SD – standard diet – dieta standardowa
HFD – high fat – dieta wysokotłuszczowa
TLR4/MyD88/NFκB – szlak sygnałowy Toll-like receptor 4/mieloidalny czynnik różnicowania 88/czynnik jądrowy-κB
BMI – Body Mass Index – wskaźnik masy ciała
hs-CRP – białko C-reaktywne o wysokiej czułości
RBP4 – białko wiążące retinol typu 4
SREBP-1 – sterol regulatory element-binding protein – białko wiążące czynnik regulujący sterole typu 1
IGT – impaired glucose tolerance – upośledzona tolerancja glukozy
IS – insulin sensitivity
LC-PUFA n-3 – long-chain n-3 polyunsaturated fatty acids
MUFAs – mono-unsaturated fatty acids – jednonienasycone kwasy tłuszczowe
PUFAs – polyunsaturated fatty acids – wielonienasycone kwasy tłuszczowe
VLDL-TG – lipoproteina o bardzo niskiej gęstości
FAS – fatty acid synthase – syntaza kwasów tłuszczowych
REFERENCJE (70)
1.
Dhanya R. Quercetin for managing type 2 diabetes and its complications, an insight into multitarget therapy. Biomed Pharmacother. 2022;146:112560.
2.
Pivari F, Mingione A, Brasacchio C, et al. Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment. Nutrients. 2019;11(8):1837.
3.
Kowalska H, Lenart A, Marzec A, et al. Wykorzystanie produktów prozdrowotnych i suplementów diety w insulinooporności. Postępy Techniki Przetwórstwa Spożywczego. 2017;2/2017:46–55.
4.
Kunnumakkara AB, Bordoloi D, Padmavathi G, et al. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol. 2017;174(11):1325–1348.
5.
Stani´c Z. Curcumin, a Compound from Natural Sources, a True Scientific Challenge—A Review. Plant Foods Hum Nutr. 2017;72(1):1–12.
6.
Lin J, Zheng S, Chen A. Curcumin attenuates the effects of insulin on stimulating hepatic stellate cell activation by interrupting insulin signaling and attenuating oxidative stress. Lab Invest. 2009;89(12):1397–409.
7.
Srivastava RA, Pinkosky SL, Filippov S, et al. AMP-activated protein kinase: An emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases. J Lipid Res. 2012;53(12):2490–514.
8.
Kim JH, Park JM, Kim EK, et al. Curcumin stimulates glucose uptake through AMPK-p38 MAPK pathways in L6 myotube cells. J Cell Physiol. 2010;223(3):771–8.
9.
Cicero AF, Sahebkar A, Fogacci F, et al. Effects of phytosomal curcumin on anthropometric parameters, insulin resistance, cortisolemia and nonalcoholic fatty liver disease indices: a double-blind, placebocontrolled clinical trial. Eur J Nutr. 2020;59(2):477–483.
10.
Heshmati J, Moini A, Sepidarkish M, et al. Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial. Phytomedicine. 2020;.
11.
Gutierres VO, Assis RP, Arcaro CA, et al. Curcumin improves the effect of a reduced insulin dose on glycemic control and oxidative stress in streptozotocin-diabetic rats. Phyther Res. 2019; 33(4):976–988.
12.
Jacob A, WU R, Zhou M, et al. Mechanism of the anti-inflammatory effect of curcumin: PPAR-gamma activation. PPAR Res. 2007; 2007:89369.
13.
Jamilian M, Foroozanfard F, Kavossian E, et al. Effects of curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Clin Nutr ESPEN. 2020; 36:128–133.
14.
Chien Y, Chang Ch, Wu M, et al. Effects of Curcumin on Glycemic Control and Lipid Profile in Polycystic Ovary Syndrome: Systematic Review with MetaAnalysis and Trial Sequential Analysis. Nutrients. 2021; 13(2):684.
15.
Heshmati J, Golab F, Morvaridzadeh M, et al. The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor ? coactivator 1? gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial. Diabetes Metab Syndr. 2020; 14(2):77–82.
16.
Gao L, Gu Y, Yin X. High serum tumor necrosis factor-alpha levels in women with polycystic ovary syndrome: A meta-analysis. PLoS One. 2016; 11(10):e0164021.
17.
Dieplinger H, Dieplinger B. Afamin – A pleiotropic glycoprotein involved in various disease states. Clin Chim Acta. 2015; 446:105–10.
18.
Kheiripour N, Khodamoradi Z, Ranjbar A, et al. The positive effect of short-term nano-curcumin therapy on insulin resistance and serum levels of afamin in patients with metabolic syndrome. Avicenna J Phytomed. 2021; 11(2):146–153.
19.
Rahimi HR, Mohammadpour AH, Dastani M, et al. The effect of nanocurcumin on HbA1c, fasting blood glucose, and lipid profile in diabetic subjects: a randomized clinical trial. Avicenna J Phytomed. 2016; 6(5):567–577.
20.
Hatamipour M, Sahebkar A, Alavizadeh SH, et al. Novel nanomicelle formulation to enhance bioavailability and stability of curcuminoids. Iran J Basic Med Sci. 2019; 22(3):282–289.
21.
Panahi Y, Khalili N, Sahebi E, et al. Effects of curcuminoids plus piperine on glycemic, hepatic and inflammatory biomarkers in patients with type 2 diabetes mellitus: a randomized double-blind placebo-controlled trial. Drug Res. 2018; 68(07):403–409.
22.
Asadi S, Gholami MS, Siassi F, et al. Beneficial effects of nano-curcumin supplement on depression and anxiety in diabetic patients with peripheral neuropathy: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2020; 34(4):896–903.
23.
Thota RN, Acharya SH, Garg ML. Curcumin and/or omega-3 polyunsaturated fatty acids supplementation reduces insulin resistance and blood lipids in individuals with high risk of type 2 diabetes: a randomised controlled trial. Lipids Health and Dis. 2019; 18(1):p.31.
24.
Adibian M, Hodaei H, Nikpayam O, et al. The effects of curcumin supplementation on high-sensitivity C-reactive protein, serum adiponectin, and lipid profile in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Phytother Res. 2019; 33(5):1374–1383.
25.
Panahi Y, Khalili N, Sahebi E, et al. Curcuminoids Plus Piperine Modulate Adipokines in Type 2 Diabetes Mellitus. Curr Clin Pharmacol. 2018; 12(4):253–258.
26.
Pourhabibi-Zarandi F, Rafraf M, Zayeni H, et al. Effects of curcumin supplementation on metabolic parameters, inflammatory factors and obesity values in women with rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2022; 36(4):1797–1806.
27.
Panaro MA, Corrado A, Benameur T, et al. The emerging role of curcumin in the modulation of TLR-4 signaling pathway: Focus on neuroprotective and anti-rheumatic properties. Int J Mol Sci. 2020; 21(7): 2299.
28.
Lachowicz M, Stańczak A, Kołodziejczyk M. Kurkumina – naturalny polifenol o wielu właściwościach – rozwiązania technologiczne wspomagające farmakoterapię. Farm Pol. 2020; 76(11): 603–610.
29.
Wang K, Feng X, Chai L, et al. The metabolism of berberine and its contribution to the pharmacological effects. Drug Metab Rev. 2017; 49(2)139–157.
30.
Xu X, Yi H, Wu J, et al. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed Pharmacother. 2021; 133:110984.
31.
Yin J, Gao Z, Liu D, et al. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab. 2008; 294(1):E148–56.
32.
Chandirasegaran G, Elanchezhiyan C, Ghosh K, et al. Berberine chloride ameliorates oxidative stress, inflammation and apoptosis in the pancreas of Streptozotocin induced diabetic rats. Biomed Pharmacother. 2017; 95:175–185.
33.
Ma X, Chen Z, Wang L, et al. The pathogenesis of diabetes mellitus by oxidative stress and inflammation: its inhibition by berberine. Front Pharmacol. 2018; 9:782.
34.
Gong J, Li J, Dong H, et al. Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88. BMC Complement Altern Med. 2019; 19(1):314.
35.
Mo C, Wang L, Zhang J, et al. The crosstalk between Nrf2 and AMPK signal pathways is important for the anti-inflammatory effect of berberine in LPS stimulated macrophages and endotoxin-shocked mice. Antioxid Redox Signal. 2014; 20(4):574–88.
36.
Jiang SJ, Dong H, Li JB, et al. Berberine inhibits hepatic gluconeogenesis via the LKB1-AMPK-TORC2 signaling pathway in streptozotocininduced diabetic rats. World J Gastroenterol. 2015; 21(25):7777–85.
37.
Li A, Lin C, Xie F, et al. Berberine Ameliorates Insulin Resistance by Inhibiting IKK/NF-?B, JNK, and IRS-1/AKT Signaling Pathway in Liver of Gestational Diabetes Mellitus Rats. Metab Syndr Relat Disord. 2022; 20(8):480–488.
38.
Zhong Y, Jin J, Liu P, et al. Berberine attenuates hyperglycemia by inhibiting the hepatic glucagon pathway in diabetic mice. Oxid Med Cell Longev. 2020; 2020:6210526.
39.
He R, Chen Y, Cai Q. The Role of the LTB4-BLT1 axis in Health and Disease. Pharmacol Res. 2020; 158:104857.
40.
Gong M, Duan H, Wu F, et al. Berberine Alleviates Insulin Resistance and Inflammation via Inhibiting the LTB4–BLT1 Axis. Front Pharmacol. 2021; 12:722360.
41.
Mao ZJ, Lin M, Zhang X, et al. Combined Use of Astragalus Polysaccharide and Berberine Attenuates Insulin Resistance in IR HepG2 Cells via Regulation of the Gluconeogenesis Signaling Pathway. Front Pharmacol. 2019; 10:1508.
42.
Cui HX, Hu YN, Li JW, et al. Hypoglycemic mechanism of the berberine organic acid salt under the synergistic effect of intestinal flora and oxidative stress. Oxid Med Cell Longev. 2018; 2018:8930374.
43.
Zhang W, Xu JH, Yu T, et al. Effects of berberine and metformin on intestinal inflammation and gut microbiome composition in db/db mice. Biomed Pharmacother. 2019; 118:109131.
44.
Yue SJ, Liu J, Wang AT, et al. Berberine alleviates insulin resistance by reducing peripheral branched-chain amino acids. Am J Physiol Endocrinol Metab. 2019; 316(1):E73-E85.
45.
Yao Y, Chen Ch, Yan L, et al. Berberine alleviates type 2 diabetic symptoms by altering gut microbiota and reducing aromatic amino acids. Biomed Pharmacother. 2020; 131:110669.
46.
Lupo MG, Brilli E, De Vito V, et al. In Vitro and In Vivo Sucrosomial® Berberine Activity on Insulin Resistance. Nutrients. 2022; 14(17):3595.
47.
Liu D, Zhang Y, Liu Y, et al. Berberine modulates gut microbiota and reduces insulin resistance via the TLR4 signaling pathway. Exp Clin Endocrinol Diabetes. 2018; 126(8):513–520.
48.
Furrianca MC, Alvear M, Zambrano T, et al. Hypoglycemic effect of Berberis microphylla G Forst root extract. Trop J Pharm Res. 2017; 16(9):2179–2184.
49.
Chen L, Lu W, Li Y. Berberine ameliorates type 2 diabetes via modulation of Bifidobacterium species, tumor necrosis factor-?, and lipopolysaccharide. Int J Clin Exp Med. 2016; 9(6):9365–9372.
50.
Mróz M, Pastusiak K, Bogdański P. Potencjalne możliwości wykorzystania berberyny w przeciwdziałaniu insulinooporności i w cukrzycy typu 2. Postępy Higieny i Medycyny Doświadczalnej. 2021; 75(1): 790–801.
51.
Słoma M, Szeja N. Wpływ antocyjanów na insulinooporność. Forum Zaburzeń Metab. 2018; 9(4): 175–181.
52.
Baum J, Howard L, Prior R, et al. Effect of Aronia melanocarpa (Black Chokeberry) supplementation on the development of obesity in mice fed a high-fat diet. J Berry Res. 2016; 6(2): 203–212.
53.
Esposito D, Damsud T, Wilson M, et al. Black Currant Anthocyanins Attenuate Weight Gain and Improve Glucose Metabolism in Diet Induced Obese Mice with Intact, but Not Disrupted, Gut Microbiome. J Agric Food Chem. 2015; 63(27): 6172–6180.
54.
Jennings A, Welch AA, Spector T, et al. Intakes of anthocyanins and flavones are associated with biomarkers of insulin resistance and inflammation in women. J Nutr. 2014; 144(2): 202–208.
55.
Li D, Zhang Y, Liu Y, et al. Purified anthocyanin supplementation reduces dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients. J Nutr. 2015; 145(4): 742–748.
56.
Xu H, Luo J, Huang J, et al. Flavonoids intake and risk of type 2 diabetes mellitus: A meta-analysis of prospective cohort studies. Medicine. 2018; 97(19), e0686.
57.
Guarino G, Della Corte T, Strollo F, et al. Policaptil Gel Retard in adult subjects with the metabolic syndrome: Efficacy, safety, and tolerability compared to metformin. Diabetes Metab Syndr. 2021; 15 (3) 901–907.
58.
Stagi S, Lapi E, Seminara S, et al. Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM. Ital J Pediatr. 2015; 41(1), 10.
59.
Greco CM, Garetto S, Montellier E, et al. A non-pharmacological therapeutic approach in the gut triggers distal metabolic rewiring capable of ameliorating diet-induced dysfunctions encompassed by metabolic syndrome. Sci Rep. 2020; 10(1):12915.
60.
Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017; 60(9):1620e9.
61.
Thota RN, Acharya SH, Garg ML. Curcumin and/or omega-3 polyunsaturated fatty acids supplementation reduces insulin resistance and blood lipids in individuals with high risk of type 2 diabetes: a randomised controlled trial. Lipids Health Dis. 2019; 18(1).
62.
Diolintzi A, Panagiotakos D, Sidossis L. From Mediterranean diet to Mediterranean lifestyle: A narrative review. Public Health Nutr. 2019; 22(14):2703–2713.
63.
Kim H, Caulfield LE, Garcia-Larsen V, et al. Plant-Based Diets Are Associated with a Lower Risk of Incident Cardiovascular Disease, Cardiovascular Disease Mortality, and All-Cause Mortality in a General Population of Middle-Aged Adults. J Am Heart Assoc. 2019; 8(16):e012865.
64.
Qian F, Korat AA, Malik V, et al. Metabolic Effects of Monounsaturated Fatty Acid-Enriched Diets Compared with Carbohydrate or Polyunsaturated Fatty Acid Enriched Diets in Patients with Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Diabetes Care. 2016; 39(8):1448–57.
65.
Mirabelli M, Chiefari E, Arcidiacono B, et al. Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases. Nutrients. 2020; 12(4):1066;.
66.
Sundstrom L, Myhre S, Sundqvist M, et al. The acute glucose lowering effect of specific GPR120 activation in mice is mainly driven by glucagon-like peptide 1. PLoS One. 2017; 12(12):e0189060.
67.
Infante M, Leoni M, Caprio M, et al. Longterm metformin therapy and vitamin B12 deficiency: An association to bear in mind. World J Diabetes. 2021; 12(7):916–931.
68.
Halczuk K, Karwowski B. Witamina B12 – czy jest nam potrzebna? Farm Pol. 2022; 78(9): 527–535.
69.
Ashok T, Puttam H, Tarnate VCA, et al. Role of Vitamin B12 and Folate in Metabolic Syndrome Cureus. 2021; 13(10):e18521.
70.
Satapathya S, Bandyopadhyayb D, Patroc BD, et al. Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial. Complement Ther Med. 2020; 53:102526.