Research Article
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Year 2025, Volume: 44 Issue: 2, 81 - 89, 31.12.2025
https://doi.org/10.30782/jrvm.1703629

Abstract

References

  • Lynn J, Park M, Ogunwale C, Acquaah-Mensah GK. A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer's Disease. J Alzheimers Dis. 2022;85(2):485-501. doi:10.3233/JAD-210612
  • Patel V, Edison P. Cardiometabolic risk factors and neurodegeneration: a review of the mechanisms underlying diabetes, obesity and hypertension in Alzheimer's disease. J Neurol Neurosurg Psychiatry. May 14 2024;95(6):581-589. doi:10.1136/jnnp-2023-332661
  • Steen E, Terry BM, Rivera EJ, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? J Alzheimers Dis. Feb 2005;7(1):63-80. doi:10.3233/jad-2005-7107
  • Shieh JC, Huang PT, Lin YF. Alzheimer's Disease and Diabetes: Insulin Signaling as the Bridge Linking Two Pathologies. Mol Neurobiol. Apr 2020;57(4):1966-1977. doi:10.1007/s12035-019-01858-5
  • Acun AD, Kantar D, Er H, Erkan O, Derin N, Yargicoglu P. Investigation of Cyclo-Z Therapeutic Effect on Insulin Pathway in Alzheimer's Rat Model: Biochemical and Electrophysiological Parameters. Mol Neurobiol. Jul 2023;60(7):4030-4048. doi:10.1007/s12035-023-03334-7
  • Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. May 2004;61(5):661-6. doi:10.1001/archneur.61.5.661
  • Harvey J. Leptin regulation of neuronal morphology and hippocampal synaptic function. Front Synaptic Neurosci. 2013;5:3. doi:10.3389/fnsyn.2013.00003
  • Fewlass DC, Noboa K, Pi-Sunyer FX, Johnston JM, Yan SD, Tezapsidis N. Obesity-related leptin regulates Alzheimer's Abeta. Faseb j. Dec 2004;18(15):1870-8. doi:10.1096/fj.04-2572com
  • Paz-Filho G, Mastronardi C, Franco CB, Wang KB, Wong ML, Licinio J. Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arq Bras Endocrinol Metabol. Dec 2012;56(9):597-607. doi:10.1590/s0004-27302012000900001
  • 1Dostalova I, Haluzikova D, Haluzik M. Fibroblast growth factor 21: a novel metabolic regulator with potential therapeutic properties in obesity/type 2 diabetes mellitus. Physiol Res. 2009;58(1):1-7. doi:10.33549/physiolres.931610
  • Fon Tacer K, Bookout AL, Ding X, et al. Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol. Oct 2010;24(10):2050-64. doi:10.1210/me.2010-0142
  • Sa-Nguanmoo P, Chattipakorn N, Chattipakorn SC. Potential roles of fibroblast growth factor 21 in the brain. Metab Brain Dis. Apr 2016;31(2):239-48. doi:10.1007/s11011-015-9789-3
  • Hsuchou H, Pan W, Kastin AJ. The fasting polypeptide FGF21 can enter brain from blood. Peptides. Dec 2007;28(12):2382-6. doi:10.1016/j.peptides.2007.10.007
  • Lan T, Morgan DA, Rahmouni K, et al. FGF19, FGF21, and an FGFR1/beta-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia. Cell Metab. Nov 7 2017;26(5):709-718 e3. doi:10.1016/j.cmet.2017.09.005
  • Owen BM, Ding X, Morgan DA, et al. FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab. Oct 7 2014;20(4):670-7. doi:10.1016/j.cmet.2014.07.012
  • Bookout AL, de Groot MH, Owen BM, et al. FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat Med. Sep 2013;19(9):1147-52. doi:10.1038/nm.3249
  • Xu J, Lloyd DJ, Hale C, et al. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes. Jan 2009;58(1):250-9. doi:10.2337/db08-0392
  • Lin Z, Tian H, Lam KS, et al. Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab. May 7 2013;17(5):779-89. doi:10.1016/j.cmet.2013.04.005
  • Anderson KE, Carroll MJ, Sheehan T, et al. Hive-stored pollen of honey bees: many lines of evidence are consistent with pollen preservation, not nutrient conversion. Mol Ecol. Dec 2014;23(23):5904-17. doi:10.1111/mec.12966
  • Doganyigit Z, Yakan B, Soylu M, Kaymak E, Okan A, Silici S. Histological, immunohistochemical and biochemical effects of bee bread on stomach tissue of obese rats. Bratisl Lek Listy. 2020;121(7):504-511. doi:10.4149/BLL_2020_083
  • Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. Apr 1991;40(4):405-12. doi:10.2337/diab.40.4.405
  • Tian Z, Wang J, Xu M, Wang Y, Zhang M, Zhou Y. Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats. Cell Physiol Biochem. 2016;40(6):1670-1677. doi:10.1159/000453216
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. May 07 1976;72:248-54. doi:S0003269776699996 [pii]
  • Khalili D, Khayamzadeh M, Kohansal K, et al. Are HOMA-IR and HOMA-B good predictors for diabetes and pre-diabetes subtypes? BMC Endocr Disord. Feb 14 2023;23(1):39. doi:10.1186/s12902-023-01291-9
  • Beamish CA, Gaber AO, Fraga DW, Hamilton DJ, Sabek OM. Pretransplant HOMA-β Is Predictive of Insulin Independence in 7 Patients With Chronic Pancreatitis Undergoing Islet Autotransplantation. Transplant Direct. Oct 2022;8(10)doi:ARTN e1367 10.1097/TXD.0000000000001367
  • Deeds MC, Anderson JM, Armstrong AS, et al. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab Anim. Jul 2011;45(3):131-40. doi:10.1258/la.2010.010090
  • Qi Z, Breyer MD. Diabetic nephropathy: big and bad. Kidney Int. Oct 2005;68(4):1896-7. doi:10.1111/j.1523-1755.2005.00614.x
  • Ruze R, Liu T, Zou X, et al. Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments. Front Endocrinol (Lausanne). 2023;14:1161521. doi:10.3389/fendo.2023.1161521
  • Koksal B. Effect of Streptozotocin on Plasma Insulin Levels of Rats and Mice: A Meta-analysis Study. Open Access Maced J Med Sci. Sep 15 2015;3(3):380-3. doi:10.3889/oamjms.2015.093
  • Andonova M, Dzhelebov P, Trifonova K, et al. Metabolic Markers Associated with Progression of Type 2 Diabetes Induced by High-Fat Diet and Single Low Dose Streptozotocin in Rats. Vet Sci. Jul 2 2023;10(7)doi:10.3390/vetsci10070431
  • Magalhães DA, Kume WT, Correia FS, et al. High-fat diet and streptozotocin in the induction of type 2 diabetes mellitus: a new proposal. An Acad Bras Cienc. Mar 21 2019;91(1):e20180314. doi:10.1590/0001-3765201920180314
  • Zafar M, Naqvi SNUH. Effects of STZ-Induced Diabetes on the Relative Weights of Kidney, Liver and Pancreas in Albino Rats: A Comparative Study. Int J Morphol. Mar 2010;28(1):135-142.
  • Saad MF, Khan A, Sharma A, et al. Physiological insulinemia acutely modulates plasma leptin. Diabetes. Apr 1998;47(4):544-9. doi:10.2337/diabetes.47.4.544
  • Mohammadzadeh G, Zarghami N. Serum leptin level is reduced in non-obese subjects with type 2 diabetes. Int J Endocrinol Metab. Winter 2013;11(1):3-10. doi:10.5812/ijem.6535
  • Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin-glucose axis. Front Neurosci. 2013;7:51. doi:10.3389/fnins.2013.00051
  • Meek TH, Morton GJ. Leptin, diabetes, and the brain. Indian J Endocrinol Metab. Dec 2012;16(Suppl 3):S534-42. doi:10.4103/2230-8210.105568
  • Hamilton K, Harvey J. The Neuronal Actions of Leptin and the Implications for Treating Alzheimer's Disease. Pharmaceuticals (Basel). Jan 11 2021;14(1)doi:10.3390/ph14010052
  • Talukdar S, Owen BM, Song P, et al. FGF21 Regulates Sweet and Alcohol Preference. Cell Metab. Feb 9 2016;23(2):344-9. doi:10.1016/j.cmet.2015.12.008
  • Douris N, Stevanovic DM, Fisher FM, et al. Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice. Endocrinology. Jul 2015;156(7):2470-81. doi:10.1210/en.2014-2001
  • Kang K, Xu P, Wang M, et al. FGF21 attenuates neurodegeneration through modulating neuroinflammation and oxidant-stress. Biomed Pharmacother. Sep 2020;129:110439. doi:10.1016/j.biopha.2020.110439
  • Craft S. Insulin resistance syndrome and Alzheimer's disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol Aging. Dec 2005;26 Suppl 1:65-9. doi:10.1016/j.neurobiolaging.2005.08.021
  • Fisher FM, Maratos-Flier E. Understanding the Physiology of FGF21. Annu Rev Physiol. 2016;78:223-41. doi:10.1146/annurev-physiol-021115-105339
  • Meex RC, Hoy AJ, Morris A, et al. Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism. Cell Metab. Dec 1 2015;22(6):1078-89. doi:10.1016/j.cmet.2015.09.023
  • Kieliszek M, Piwowarek K, Kot AM, Błażejak S, Chlebowska-Śmigiel A, Wolska I. Pollen and bee bread as new health-oriented products: A review. Trends in Food Science & Technology. 2018/01/01/ 2018;71:170-180. doi:https://doi.org/10.1016/j.tifs.2017.10.021
  • Komosinska-Vassev K, Olczyk P, Kaźmierczak J, Mencner L, Olczyk K. Bee pollen: chemical composition and therapeutic application. Evid Based Complement Alternat Med. 2015;2015:297425. doi:10.1155/2015/297425
  • El-Seedi HR, El-Wahed AAA, Salama S, et al. Natural Remedies and Health; A Review of Bee Pollen and Bee Bread Impact on Combating Diabetes and Obesity. Curr Nutr Rep. Dec 2024;13(4):751-767. doi:10.1007/s13668-024-00567-3
  • Zakaria Z, Othman ZA, Suleiman JB, et al. Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation. Antioxidants (Basel). Dec 20 2021;10(12)doi:10.3390/antiox10122031
  • Othman ZA, Wan Ghazali WS, Noordin L, Mohd Yusof NA, Mohamed M. Phenolic Compounds and the Anti-Atherogenic Effect of Bee Bread in High-Fat Diet-Induced Obese Rats. Antioxidants (Basel). Dec 30 2019;9(1)doi:10.3390/antiox9010033
  • Greco SJ, Sarkar S, Johnston JM, Tezapsidis N. Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells. Biochem Biophys Res Commun. Feb 27 2009;380(1):98-104. doi:10.1016/j.bbrc.2009.01.041
  • Lieb W, Beiser AS, Vasan RS, et al. Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. Jama. Dec 16 2009;302(23):2565-72. doi:10.1001/jama.2009.1836
  • Niedowicz DM, Studzinski CM, Weidner AM, et al. Leptin regulates amyloid β production via the γ-secretase complex. Biochim Biophys Acta. Mar 2013;1832(3):439-44. doi:10.1016/j.bbadis.2012.12.009
  • Kocot J, Kiełczykowska M, Luchowska-Kocot D, Kurzepa J, Musik I. Antioxidant Potential of Propolis, Bee Pollen, and Royal Jelly: Possible Medical Application. Oxid Med Cell Longev. 2018;2018:7074209. doi:10.1155/2018/7074209
  • Geng L, Lam KSL, Xu A. The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nat Rev Endocrinol. Nov 2020;16(11):654-667. doi:10.1038/s41574-020-0386-0
  • Jimenez V, Jambrina C, Casana E, et al. FGF21 gene therapy as treatment for obesity and insulin resistance. EMBO Molecular Medicine. 2018/08/01 2018;10(8):e8791. doi:https://doi.org/10.15252/emmm.201708791

Effects of Perga on FGF21/Leptin/Insulin in Imparied Glucose Regulation

Year 2025, Volume: 44 Issue: 2, 81 - 89, 31.12.2025
https://doi.org/10.30782/jrvm.1703629

Abstract

Objective: This study aimed to investigate the effects of Perga supplementation on glucose metabolism, body weight regulation, and amyloid-beta (Aβ) accumulation in a streptozotocin (STZ)-induced type 2 diabetes (T2D) rat model, focusing specifically on insulin, leptin, and fibroblast growth factor 21 (FGF21) signaling pathways.
Methods: Male Wistar rats were divided into Sham (S), T2D, and T2D+Perga (T2DP) groups. T2D was induced by a single intraperitoneal (i.p.) STZ injection (60 mg/kg). Perga (200 mg/kg/day) was administered to the T2DP group by gavage 14 days after diabetes induction. Plasma and brain insulin and leptin levels, liver and plasma FGF21 concentrations, Homeostasis Model Assessment of Beta Cell Function (HOMA-β) index, fasting glucose levels, body weight changes, and brain amyloid-beta (Aβ) accumulation were evaluated.
Results: STZ-induced T2D resulted in hypoinsulinemia, decreased HOMA-β scores, weight loss, reduced plasma leptin, increased brain leptin, decreased FGF21 levels, and significant Aβ accumulation in the hippocampus. Perga treatment significantly improved plasma and brain insulin levels, increased HOMA-β, reduced fasting glucose, and attenuated weight loss. Plasma leptin levels returned to normal, brain leptin levels decreased, and hippocampus Aβ burden was significantly reduced. In addition, perga supplementation almost normalized liver and plasma FGF21 levels.
Conclusion: Perga supplementation effectively ameliorates metabolic dysfunction and neurodegenerative markers in the T2D model. Its regulatory effects on insulin, leptin, and FGF21 signaling highlight its potential as a natural therapeutic agent in managing T2D and associated AD-like pathology. Further research is needed to evaluate its clinical applicability.

Ethical Statement

Akdeniz University Animal Research Ethics Local Committee (Ethics Approval Number: 2025.04.B.001)

References

  • Lynn J, Park M, Ogunwale C, Acquaah-Mensah GK. A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer's Disease. J Alzheimers Dis. 2022;85(2):485-501. doi:10.3233/JAD-210612
  • Patel V, Edison P. Cardiometabolic risk factors and neurodegeneration: a review of the mechanisms underlying diabetes, obesity and hypertension in Alzheimer's disease. J Neurol Neurosurg Psychiatry. May 14 2024;95(6):581-589. doi:10.1136/jnnp-2023-332661
  • Steen E, Terry BM, Rivera EJ, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? J Alzheimers Dis. Feb 2005;7(1):63-80. doi:10.3233/jad-2005-7107
  • Shieh JC, Huang PT, Lin YF. Alzheimer's Disease and Diabetes: Insulin Signaling as the Bridge Linking Two Pathologies. Mol Neurobiol. Apr 2020;57(4):1966-1977. doi:10.1007/s12035-019-01858-5
  • Acun AD, Kantar D, Er H, Erkan O, Derin N, Yargicoglu P. Investigation of Cyclo-Z Therapeutic Effect on Insulin Pathway in Alzheimer's Rat Model: Biochemical and Electrophysiological Parameters. Mol Neurobiol. Jul 2023;60(7):4030-4048. doi:10.1007/s12035-023-03334-7
  • Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. May 2004;61(5):661-6. doi:10.1001/archneur.61.5.661
  • Harvey J. Leptin regulation of neuronal morphology and hippocampal synaptic function. Front Synaptic Neurosci. 2013;5:3. doi:10.3389/fnsyn.2013.00003
  • Fewlass DC, Noboa K, Pi-Sunyer FX, Johnston JM, Yan SD, Tezapsidis N. Obesity-related leptin regulates Alzheimer's Abeta. Faseb j. Dec 2004;18(15):1870-8. doi:10.1096/fj.04-2572com
  • Paz-Filho G, Mastronardi C, Franco CB, Wang KB, Wong ML, Licinio J. Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arq Bras Endocrinol Metabol. Dec 2012;56(9):597-607. doi:10.1590/s0004-27302012000900001
  • 1Dostalova I, Haluzikova D, Haluzik M. Fibroblast growth factor 21: a novel metabolic regulator with potential therapeutic properties in obesity/type 2 diabetes mellitus. Physiol Res. 2009;58(1):1-7. doi:10.33549/physiolres.931610
  • Fon Tacer K, Bookout AL, Ding X, et al. Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol. Oct 2010;24(10):2050-64. doi:10.1210/me.2010-0142
  • Sa-Nguanmoo P, Chattipakorn N, Chattipakorn SC. Potential roles of fibroblast growth factor 21 in the brain. Metab Brain Dis. Apr 2016;31(2):239-48. doi:10.1007/s11011-015-9789-3
  • Hsuchou H, Pan W, Kastin AJ. The fasting polypeptide FGF21 can enter brain from blood. Peptides. Dec 2007;28(12):2382-6. doi:10.1016/j.peptides.2007.10.007
  • Lan T, Morgan DA, Rahmouni K, et al. FGF19, FGF21, and an FGFR1/beta-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia. Cell Metab. Nov 7 2017;26(5):709-718 e3. doi:10.1016/j.cmet.2017.09.005
  • Owen BM, Ding X, Morgan DA, et al. FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab. Oct 7 2014;20(4):670-7. doi:10.1016/j.cmet.2014.07.012
  • Bookout AL, de Groot MH, Owen BM, et al. FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat Med. Sep 2013;19(9):1147-52. doi:10.1038/nm.3249
  • Xu J, Lloyd DJ, Hale C, et al. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes. Jan 2009;58(1):250-9. doi:10.2337/db08-0392
  • Lin Z, Tian H, Lam KS, et al. Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab. May 7 2013;17(5):779-89. doi:10.1016/j.cmet.2013.04.005
  • Anderson KE, Carroll MJ, Sheehan T, et al. Hive-stored pollen of honey bees: many lines of evidence are consistent with pollen preservation, not nutrient conversion. Mol Ecol. Dec 2014;23(23):5904-17. doi:10.1111/mec.12966
  • Doganyigit Z, Yakan B, Soylu M, Kaymak E, Okan A, Silici S. Histological, immunohistochemical and biochemical effects of bee bread on stomach tissue of obese rats. Bratisl Lek Listy. 2020;121(7):504-511. doi:10.4149/BLL_2020_083
  • Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. Apr 1991;40(4):405-12. doi:10.2337/diab.40.4.405
  • Tian Z, Wang J, Xu M, Wang Y, Zhang M, Zhou Y. Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats. Cell Physiol Biochem. 2016;40(6):1670-1677. doi:10.1159/000453216
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. May 07 1976;72:248-54. doi:S0003269776699996 [pii]
  • Khalili D, Khayamzadeh M, Kohansal K, et al. Are HOMA-IR and HOMA-B good predictors for diabetes and pre-diabetes subtypes? BMC Endocr Disord. Feb 14 2023;23(1):39. doi:10.1186/s12902-023-01291-9
  • Beamish CA, Gaber AO, Fraga DW, Hamilton DJ, Sabek OM. Pretransplant HOMA-β Is Predictive of Insulin Independence in 7 Patients With Chronic Pancreatitis Undergoing Islet Autotransplantation. Transplant Direct. Oct 2022;8(10)doi:ARTN e1367 10.1097/TXD.0000000000001367
  • Deeds MC, Anderson JM, Armstrong AS, et al. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab Anim. Jul 2011;45(3):131-40. doi:10.1258/la.2010.010090
  • Qi Z, Breyer MD. Diabetic nephropathy: big and bad. Kidney Int. Oct 2005;68(4):1896-7. doi:10.1111/j.1523-1755.2005.00614.x
  • Ruze R, Liu T, Zou X, et al. Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments. Front Endocrinol (Lausanne). 2023;14:1161521. doi:10.3389/fendo.2023.1161521
  • Koksal B. Effect of Streptozotocin on Plasma Insulin Levels of Rats and Mice: A Meta-analysis Study. Open Access Maced J Med Sci. Sep 15 2015;3(3):380-3. doi:10.3889/oamjms.2015.093
  • Andonova M, Dzhelebov P, Trifonova K, et al. Metabolic Markers Associated with Progression of Type 2 Diabetes Induced by High-Fat Diet and Single Low Dose Streptozotocin in Rats. Vet Sci. Jul 2 2023;10(7)doi:10.3390/vetsci10070431
  • Magalhães DA, Kume WT, Correia FS, et al. High-fat diet and streptozotocin in the induction of type 2 diabetes mellitus: a new proposal. An Acad Bras Cienc. Mar 21 2019;91(1):e20180314. doi:10.1590/0001-3765201920180314
  • Zafar M, Naqvi SNUH. Effects of STZ-Induced Diabetes on the Relative Weights of Kidney, Liver and Pancreas in Albino Rats: A Comparative Study. Int J Morphol. Mar 2010;28(1):135-142.
  • Saad MF, Khan A, Sharma A, et al. Physiological insulinemia acutely modulates plasma leptin. Diabetes. Apr 1998;47(4):544-9. doi:10.2337/diabetes.47.4.544
  • Mohammadzadeh G, Zarghami N. Serum leptin level is reduced in non-obese subjects with type 2 diabetes. Int J Endocrinol Metab. Winter 2013;11(1):3-10. doi:10.5812/ijem.6535
  • Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin-glucose axis. Front Neurosci. 2013;7:51. doi:10.3389/fnins.2013.00051
  • Meek TH, Morton GJ. Leptin, diabetes, and the brain. Indian J Endocrinol Metab. Dec 2012;16(Suppl 3):S534-42. doi:10.4103/2230-8210.105568
  • Hamilton K, Harvey J. The Neuronal Actions of Leptin and the Implications for Treating Alzheimer's Disease. Pharmaceuticals (Basel). Jan 11 2021;14(1)doi:10.3390/ph14010052
  • Talukdar S, Owen BM, Song P, et al. FGF21 Regulates Sweet and Alcohol Preference. Cell Metab. Feb 9 2016;23(2):344-9. doi:10.1016/j.cmet.2015.12.008
  • Douris N, Stevanovic DM, Fisher FM, et al. Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice. Endocrinology. Jul 2015;156(7):2470-81. doi:10.1210/en.2014-2001
  • Kang K, Xu P, Wang M, et al. FGF21 attenuates neurodegeneration through modulating neuroinflammation and oxidant-stress. Biomed Pharmacother. Sep 2020;129:110439. doi:10.1016/j.biopha.2020.110439
  • Craft S. Insulin resistance syndrome and Alzheimer's disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol Aging. Dec 2005;26 Suppl 1:65-9. doi:10.1016/j.neurobiolaging.2005.08.021
  • Fisher FM, Maratos-Flier E. Understanding the Physiology of FGF21. Annu Rev Physiol. 2016;78:223-41. doi:10.1146/annurev-physiol-021115-105339
  • Meex RC, Hoy AJ, Morris A, et al. Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism. Cell Metab. Dec 1 2015;22(6):1078-89. doi:10.1016/j.cmet.2015.09.023
  • Kieliszek M, Piwowarek K, Kot AM, Błażejak S, Chlebowska-Śmigiel A, Wolska I. Pollen and bee bread as new health-oriented products: A review. Trends in Food Science & Technology. 2018/01/01/ 2018;71:170-180. doi:https://doi.org/10.1016/j.tifs.2017.10.021
  • Komosinska-Vassev K, Olczyk P, Kaźmierczak J, Mencner L, Olczyk K. Bee pollen: chemical composition and therapeutic application. Evid Based Complement Alternat Med. 2015;2015:297425. doi:10.1155/2015/297425
  • El-Seedi HR, El-Wahed AAA, Salama S, et al. Natural Remedies and Health; A Review of Bee Pollen and Bee Bread Impact on Combating Diabetes and Obesity. Curr Nutr Rep. Dec 2024;13(4):751-767. doi:10.1007/s13668-024-00567-3
  • Zakaria Z, Othman ZA, Suleiman JB, et al. Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation. Antioxidants (Basel). Dec 20 2021;10(12)doi:10.3390/antiox10122031
  • Othman ZA, Wan Ghazali WS, Noordin L, Mohd Yusof NA, Mohamed M. Phenolic Compounds and the Anti-Atherogenic Effect of Bee Bread in High-Fat Diet-Induced Obese Rats. Antioxidants (Basel). Dec 30 2019;9(1)doi:10.3390/antiox9010033
  • Greco SJ, Sarkar S, Johnston JM, Tezapsidis N. Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells. Biochem Biophys Res Commun. Feb 27 2009;380(1):98-104. doi:10.1016/j.bbrc.2009.01.041
  • Lieb W, Beiser AS, Vasan RS, et al. Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. Jama. Dec 16 2009;302(23):2565-72. doi:10.1001/jama.2009.1836
  • Niedowicz DM, Studzinski CM, Weidner AM, et al. Leptin regulates amyloid β production via the γ-secretase complex. Biochim Biophys Acta. Mar 2013;1832(3):439-44. doi:10.1016/j.bbadis.2012.12.009
  • Kocot J, Kiełczykowska M, Luchowska-Kocot D, Kurzepa J, Musik I. Antioxidant Potential of Propolis, Bee Pollen, and Royal Jelly: Possible Medical Application. Oxid Med Cell Longev. 2018;2018:7074209. doi:10.1155/2018/7074209
  • Geng L, Lam KSL, Xu A. The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nat Rev Endocrinol. Nov 2020;16(11):654-667. doi:10.1038/s41574-020-0386-0
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There are 54 citations in total.

Details

Primary Language English
Subjects Veterinary Sciences (Other)
Journal Section Research Article
Authors

Alev Duygu Kuzzu 0000-0003-1240-6342

Ebru Afşar 0000-0002-7817-855X

Erdem Aslan 0000-0002-4992-5915

Serkan Uslu 0000-0002-0875-5905

Submission Date May 21, 2025
Acceptance Date December 11, 2025
Publication Date December 31, 2025
Published in Issue Year 2025 Volume: 44 Issue: 2

Cite

APA Kuzzu, A. D., Afşar, E., Aslan, E., Uslu, S. (2025). Effects of Perga on FGF21/Leptin/Insulin in Imparied Glucose Regulation. Journal of Research in Veterinary Medicine, 44(2), 81-89. https://doi.org/10.30782/jrvm.1703629
AMA Kuzzu AD, Afşar E, Aslan E, Uslu S. Effects of Perga on FGF21/Leptin/Insulin in Imparied Glucose Regulation. J Res Vet Med. December 2025;44(2):81-89. doi:10.30782/jrvm.1703629
Chicago Kuzzu, Alev Duygu, Ebru Afşar, Erdem Aslan, and Serkan Uslu. “Effects of Perga on FGF21 Leptin Insulin in Imparied Glucose Regulation”. Journal of Research in Veterinary Medicine 44, no. 2 (December 2025): 81-89. https://doi.org/10.30782/jrvm.1703629.
EndNote Kuzzu AD, Afşar E, Aslan E, Uslu S (December 1, 2025) Effects of Perga on FGF21/Leptin/Insulin in Imparied Glucose Regulation. Journal of Research in Veterinary Medicine 44 2 81–89.
IEEE A. D. Kuzzu, E. Afşar, E. Aslan, and S. Uslu, “Effects of Perga on FGF21/Leptin/Insulin in Imparied Glucose Regulation”, J Res Vet Med, vol. 44, no. 2, pp. 81–89, 2025, doi: 10.30782/jrvm.1703629.
ISNAD Kuzzu, Alev Duygu et al. “Effects of Perga on FGF21 Leptin Insulin in Imparied Glucose Regulation”. Journal of Research in Veterinary Medicine 44/2 (December2025), 81-89. https://doi.org/10.30782/jrvm.1703629.
JAMA Kuzzu AD, Afşar E, Aslan E, Uslu S. Effects of Perga on FGF21/Leptin/Insulin in Imparied Glucose Regulation. J Res Vet Med. 2025;44:81–89.
MLA Kuzzu, Alev Duygu et al. “Effects of Perga on FGF21 Leptin Insulin in Imparied Glucose Regulation”. Journal of Research in Veterinary Medicine, vol. 44, no. 2, 2025, pp. 81-89, doi:10.30782/jrvm.1703629.
Vancouver Kuzzu AD, Afşar E, Aslan E, Uslu S. Effects of Perga on FGF21/Leptin/Insulin in Imparied Glucose Regulation. J Res Vet Med. 2025;44(2):81-9.