|
|
罗伊氏乳酸杆菌(Lactobacillus reuteri) GKD2改善高脂高糖饮食动物模式之血糖调控
|
Abstract:
葡萄糖耐受不良(impaired glucose tolerance)系指生理对血糖调控能力较差的状态，虽无明显临床症状，却为糖尿病(diabetes)或心血管疾病(cardiovascular diseases)的病变前兆。此阶段往往被忽视，或医疗建议的饮食控制与运动对于此类族群的实施效果有限。益生菌(probiotics)系指对人体机能有益的细菌，可参与人体的生理代谢、肠道菌相调整等，广受市场接受，因此具应用于糖尿病病变前期对策的潜能。本实验以高脂、高糖(high fat-high sugar, HF-HS)的饮食方式诱导C57BL/6JNarl小鼠发生葡萄糖耐受不良的状况，模拟常见之葡萄糖耐受不良成因。HF-HS小鼠分别补充8周低剂量(20.5 mg/kg/day)与高剂量(102.5 mg/kg/day)的罗伊氏乳酸杆菌(Lactobacillus reuteri) GKD2菌粉。在口服葡萄糖耐受性试验(oral glucose toerance test)中，相比单纯HF-HS饮食组，摄入菌株GKD2的HF-HS小鼠，其餐后血糖值有较低的趋势。此外，血糖调节的相关指标瘦体素(leptin)在益生菌组观察到下降的趋势；非空腹的胰岛素(insulin)浓度以高剂量GKD2组呈显著下降(p < 0.05)。血脂方面，益生菌GKD2的补充显著降低血液中总胆固醇(total cholesterol)的含量(p < 0.05)。组织病理学上，观测到较少的脂肪堆积于GKD2组的小鼠肝脏组织。总观以上结果，L. reuteri GKD2有助于高脂高糖饮食者的血糖调控与生理代谢。
Impaired glucose tolerance refers to a state of poor physiological ability to regulate blood sugar. Although there are no obvious clinical symptoms, it is a precursor to diabetes or cardiovascular diseases. This stage is often ignored, or medically recommended diet control and exercise have limited effect on this group of people. Probiotics refer to bacteria that are beneficial to human body functions. They can participate in the body’s physiological metabolism and balance the gut microbiota. They are widely accepted by the market and therefore have the potential to be used in early stage countermeasures for diabetes. In this experiment, a high-fat, high-sugar (HF-HS) diet was used to induce glucose intolerance in C57BL/6JNarl mice, simulating the common causes of glucose intolerance. HF-HS mice were supplemented with low-dose (20.5 mg/kg/day) and high-dose (102.5 mg/kg/day) Lactobacillus reuteri GKD2 bacterial powder respectively for 8 weeks. In the oral glucose tolerance test, compared with the simple HF-HS diet group, the postprandial blood glucose levels of HF-HS mice consuming strain GKD2 tended to be lower. In addition, leptin, a related marker of blood sugar regulation, showed a downward trend in the probiotic group; non-fasting insulin concentration showed a significant decrease in the high-dose GKD2 group (p < 0.05). In terms of blood lipids, probiotic GKD2 supplementation significantly reduced the total cholesterol content in the blood (p < 0.05). Histopathologically, less fat accumulation was observed in the liver tissue of mice in the GKD2 group. Taken together, the above results indicated that L. reuteri GKD2 contributes to blood sugar regulation and physiological metabolism in those high-fat and high-sugar diets.
| [1] | Rao, S.S., Disraeli, P. and McGregor, T. (2004) Impaired Glucose Tolerance and Impaired Fasting Glucose. American Family Physician, 69, 1961-1968. |
| [2] | World Health Organization (1999) Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Part 1, Diagnosis and Classification of Diabetes Mellitus (No. WHO/NCD/NCS/99.2). Geneva. |
| [3] | Weiss, R., Dufour, S., Taksali, S.E., Tamborlane, W.V., Petersen, K.F., Bonadonna, R.C., Boselli, L., Barbetta, G., Allen, K., Rife, F., Savoye, M., Dziura, J., Sherwin, R., Shulman, G.I. and Caprio, S. (2003) Prediabetes in Obese Youth: A Syndrome of Impaired Glucose Tolerance, Severe Insulin Resistance, and Altered Myocellular and Abdominal Fat Partitioning. The Lancet, 362, 951-957. https://doi.org/10.1016/S0140-6736(03)14364-4 |
| [4] | Bock, G., Dalla Man, C., Campioni, M., Chittilapilly, E., Basu, R., Toffolo, G., Cobelli, C. and Rizza, R. (2006) Pathogenesis of Pre-Diabetes: Mechanisms of Fasting and Postprandial Hyperglycemia in People with Impaired Fasting Glucose and/or Impaired Glucose Tolerance. Diabetes, 55, 3536-3549. https://doi.org/10.2337/db06-0319 |
| [5] | Ko, G.T., Li, J.K., Cheung, A.Y. and Yeung, V.T. (1999) Two-Hour Post-Glucose Loading Plasma Glucose Is the Main Determinant for the Progression from Impaired Glucose Tolerance to Diabetes in Hong Kong Chinese. Diabetes Care, 22, 2096-2097. https://doi.org/10.2337/diacare.22.12.2096 |
| [6] | Gong, Q., Zhang, P., Wang, J., Ma, J., An, Y., Chen, Y., Zhang, B., Feng, X., Li, H., Chen, X., Cheng, Y.J., Gregg, E.W., Hu, Y., Bennett, P.H. and Li, G. (2019) Morbidity and Mortality after Lifestyle Intervention for People with Impaired Glucose Tolerance: 30-Year Results of the Da Qing Diabetes Prevention Outcome Study. The Lancet Diabetes & Endocrinology, 7, 452-461. https://doi.org/10.1016/S2213-8587(19)30093-2 |
| [7] | Cai, X., Zhang, Y., Li, M., Wu, J.H., Mai, L., Li, J., Yang, Y., Hu, Y. and Huang, Y. (2020) Association between Prediabetes and Risk of All Cause Mortality and Cardiovascular Disease: Updated Meta-Analysis. BMJ, 370, m2297. https://doi.org/10.1136/bmj.m2297 |
| [8] | Neves, J.S., Newman, C., Bostrom, J.A., Buysschaert, M., Newman, J.D., Medina, J.L., Goldberg, I.J. and Bergman, M. (2022) Management of Dyslipidemia and Atherosclerotic Cardiovascular Risk in Prediabetes. Diabetes Research and Clinical Practice, 190, Article 109980. https://doi.org/10.1016/j.diabres.2022.109980 |
| [9] | Feskens, E.J., Virtanen, S.M., R？s？nen, L., Tuomilehto, J., Stengard, J., Pekkanen, J., Nissinen, A. and Kromhout, D. (1995) Dietary Factors Determining Diabetes and Impaired Glucose Tolerance: A 20-Year Follow-Up of the Finnish and Dutch Cohorts of the Seven Countries Study. Diabetes Care, 18, 1104-1112. https://doi.org/10.2337/diacare.18.8.1104 |
| [10] | Saxena, R., Hivert, M.F., Langenberg, C., et al. (2010) Genetic Variation in GIPR Influences the Glucose and Insulin Responses to an Oral Glucose Challenge. Nature Genetics, 42, 142-148. https://doi.org/10.1038/ng.521 |
| [11] | Crapo, P.A., Kolterman, O.G. and Olefsky, J.M. (1980) Effects of Oral Fructose in Normal, Diabetic, and Impaired Glucose Tolerance Subjects. Diabetes Care, 3, 575-581. https://doi.org/10.2337/diacare.3.5.575 |
| [12] | La Fleur, S., Luijendijk, M.C.M., Van Rozen, A.J., Kalsbeek, A. and Adan, R.A.H. (2011) A Free-Choice High-Fat High-Sugar Diet Induces Glucose Intolerance and Insulin Unresponsiveness to a Glucose Load Not Explained by Obesity. International Journal of Obesity, 35, 595-604. https://doi.org/10.1038/ijo.2010.164 |
| [13] | Rahman, M.S., Hossain, K.S., Das, S., Kundu, S., Adegoke, E.O., Rahman, M.A., Hannan, M.A., Uddin, M.J. and Pang, M.G. (2021) Role of Insulin in Health and Disease: An Update. International Journal of Molecular Sciences, 22, Article 6403. https://doi.org/10.3390/ijms22126403 |
| [14] | Abdul-Ghani, M.A., Tripathy, D. and Defronzo, R.A. (2006) Contributions of β-Cell Dysfunction and Insulin Resistance to the Pathogenesis of Impaired Glucose Tolerance and Impaired Fasting Glucose. Diabetes Care, 29, 1130-1139. https://doi.org/10.2337/dc05-2179 |
| [15] | Ca？ete, R., Gil-Campos, M., Aguilera, C.M. and Gil, A. (2007) Development of Insulin Resistance and Its Relation to Diet in the Obese Child. European Journal of Nutrition, 46, 181-187. https://doi.org/10.1007/s00394-007-0648-9 |
| [16] | Tanenberg, R.J. (2004) Transitioning Pharmacologic Therapy from Oral Agents to Insulin for Type 2 Diabetes. Current Medical Research and Opinion, 20, 541-553. https://doi.org/10.1185/030079903125003134 |
| [17] | Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A.J., Gojobori, T. and Isenovic, E.R. (2021) Leptin and Obesity: Role and Clinical Implication. Frontiers in Endocrinology, 12, Article 585887. https://doi.org/10.3389/fendo.2021.585887 |
| [18] | Gruzdeva, O., Borodkina, D., Uchasova, E., Dyleva, Y. and Barbarash, O. (2019) Leptin Resistance: Underlying Mechanisms and Diagnosis. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 12, 191-198. https://doi.org/10.2147/dmso.s182406 |
| [19] | Kumar, R., Mal, K., Razaq, M.K., Magsi, M., Memon, M.K., Memon, S., Afroz, M.N., Siddiqui, H.F. and Rizwan, A. (2020) Association of Leptin with Obesity and Insulin Resistance. Cureus, 12, e12178. https://doi.org/10.7759/cureus.12178 |
| [20] | Lee, C.Y. (2007) Relationship between Adipocytokines and Insulin Resistance in Non-Diabetic Women. Master’s Thesis, Kaohsiung Medical University, Kaohsiung. |
| [21] | Johnson, J.D. (2021) On the Causal Relationships between Hyperinsulinaemia, Insulin Resistance, Obesity and Dysglycaemia in Type 2 Diabetes. Diabetologia, 64, 2138-2146. https://doi.org/10.1007/s00125-021-05505-4 |
| [22] | London, E. and Stratakis, C.A. (2022) The Regulation of PKA Signaling in Obesity and in the Maintenance of Metabolic Health. Pharmacology & Therapeutics, 237, Article 108113. https://doi.org/10.1016/j.pharmthera.2022.108113 |
| [23] | Nianogo, R.A. and Arah, O.A. (2022) Forecasting Obesity and Type 2 Diabetes Incidence and Burden: The ViLA-Obesity Simulation Model. Frontiers in Public Health, 10, Article 818816. https://doi.org/10.3389/fpubh.2022.818816 |
| [24] | Cui, J., Sun, J., Wang, W., Xin, H., Qiao, Q., Baloch, Z. and Ma, A. (2017) The Association of Triglycerides and Total Cholesterol Concentrations with Newly Diagnosed Diabetes in Adults in China. Oncotarget, 8, Article 103477. https://doi.org/10.18632/oncotarget.21969 |
| [25] | Ren, X., Chen, Z.A., Zheng, S., Han, T., Li, Y., Liu, W. and Hu, Y. (2016) Association between Triglyceride to HDL-C Ratio (TG/HDL-C) and Insulin Resistance in Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus. PLOS ONE, 11, e0154345. https://doi.org/10.1371/journal.pone.0154345 |
