Strategies for optimization of hypoglycemia rat models

Lee Yeong Zher , Eason Kong Qi Zheng , Rayneshia Elaura Raymond , Ye Zhen Jie , Christina Gertrude Yap

Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (9) : 1590 -1610.

PDF
Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (9) : 1590 -1610. DOI: 10.1002/ame2.70045
REVIEW

Strategies for optimization of hypoglycemia rat models

Author information +
History +
PDF

Abstract

This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia. We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experimental models. This study aims to investigate the therapeutic potential of phytotherapeutic agents and their efficacy in mitigating the adverse effects of hypoglycemia. Insights from our planned research will be beneficial in improving quality of life for individuals at risk of episodes of low blood sugar. Optimizing hypoglycemic rat models for research requires selecting a suitable experimental model that will be susceptible to hypoglycemia induction, effective monitoring of blood glucose levels, and maintaining a high survival rate throughout the required experimental duration.

Keywords

hypoglycemia / in vivo study / phytotherapeutic agents / rat model / therapeutic development / translational research

Cite this article

Download citation ▾
Lee Yeong Zher, Eason Kong Qi Zheng, Rayneshia Elaura Raymond, Ye Zhen Jie, Christina Gertrude Yap. Strategies for optimization of hypoglycemia rat models. Animal Models and Experimental Medicine, 2025, 8(9): 1590-1610 DOI:10.1002/ame2.70045

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Hicks D. The dangers of hypoglycaemia. Nurs Res Care. 2010; 12(1): 22-26.

[2]

Wright EE, Morgan K, Fu DK, Wilkins N, Guffey WJ. Time in range: how to measure it, how to report it, and its practical application in clinical decision-making. Clin Diabetes. 2020; 38(5): 439-448.

[3]

Lash RW, Lucas DO, Illes J. Preventing hypoglycemia in type 2 diabetes. J Clin Endocrinol Metab. 2018; 103(4): 1265-1268.

[4]

Lalic NM. The case for: hypoglycemia is of cardiovascular importance. Diabetes Care. 2013; 36(Suppl 2): S264-S266.

[5]

Meneilly GS, Tessier DM. Diabetes, dementia and hypoglycemia. Can J Diabetes. 2016; 40(1): 73-76.

[6]

Silbert R, Salcido-Montenegro A, Rodriguez-Gutierrez R, Katabi A, McCoy RG. Hypoglycemia among patients with type 2 diabetes: epidemiology, risk factors, and prevention strategies. Curr Diab Rep. 2018; 18(8): 53.

[7]

Zhang F, Ye C, Li G, et al. The rat model of type 2 diabetic mellitus and its Glycometabolism characters. Exp Anim. 2003; 52(5): 401-407.

[8]

Kottaisamy CPD, Raj DS, Prasanth Kumar V, Sankaran U. Experimental animal models for diabetes and its related complications—a review. Lab Anim Res. 2021; 37(1): 23.

[9]

Zakaria Z, Ahmad M, Qinna N. Animal models in type 2 diabetes mellitus research: pros and cons. Jordan J Agric Sci. 2021; 17: 417-432.

[10]

Acharya NK, Qi X, Goldwaser EL, et al. Retinal pathology is associated with increased blood-retina barrier permeability in a diabetic and hypercholesterolaemic pig model: beneficial effects of the LpPLA2 inhibitor Darapladib. Diab Vasc Dis Res. 2017; 14(3): 200-213.

[11]

McCrimmon RJ. Consequences of recurrent hypoglycaemia on brain function in diabetes. Diabetologia. 2021; 64(5): 971-977.

[12]

Nikpendar M, Javanbakht M, Moosavian H, et al. Effect of recurrent severe insulin-induced hypoglycemia on the cognitive function and brain oxidative status in the rats. Diabetol Metab Syndr. 2024; 16(1): 161.

[13]

Reno CM, Bayles J, Huang Y, et al. Severe hypoglycemia-induced fatal cardiac arrhythmias are mediated by the parasympathetic nervous system in rats. Diabetes. 2019; 68(11): 2107-2119.

[14]

Ramachandran S, Rajasekaran A, Manisenthilkumar KT. Investigation of hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark in diabetic rats. Asian Pac J Trop Biomed. 2012; 2(4): 262-268.

[15]

Su Y-J, Liao C-J. Hypoglycemia in emergency department. J Acute Dis. 2015; 4(1): 59-62.

[16]

Dewan N, Shukla V, Rehni AK, et al. Exposure to recurrent hypoglycemia alters hippocampal metabolism in treated streptozotocin-induced diabetic rats. CNS Neurosci Ther. 2020; 26(1): 126-135.

[17]

Luo M, Hu Y, Lv D, et al. Recurrent hypoglycemia impaired vascular function in advanced T2DM rats by inducing pyroptosis. Oxid Med Cell Longev. 2022; 2022(1): 7812407.

[18]

Guillén J, Steckler T. Good research practice: lessons from animal care and use. In: Bespalov A, Michel MC, Steckler T, eds. Good Research Practice in Non-Clinical Pharmacology and Biomedicine. Springer International Publishing; 2020: 367-382.

[19]

Homeira Z, Saleh ZA, Mohammad KGN, Mehdi H. Effect of chronic restraint stress on carbohydrate metabolism in rat. Physiol Behav. 2006; 89(3): 373-378.

[20]

Burgeiro A, Cerqueira MG, Varela-Rodríguez BM, et al. Glucose and lipid Dysmetabolism in a rat model of prediabetes induced by a high-sucrose diet. Nutrients. 2017; 9(6): 638.

[21]

Cryer PE. Minireview: glucagon in the pathogenesis of hypoglycemia and hyperglycemia in diabetes. Endocrinology. 2012; 153(3): 1039-1048.

[22]

Morton GJ, Schwartz MW. Leptin and the central nervous system control of glucose metabolism. Physiol Rev. 2011; 91(2): 389-411.

[23]

Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. Diabetes. 2005; 54(12): 3592-3601.

[24]

Gibbons CH, Adler GK, Bonyhay I, Freeman R. Experimental hypoglycemia is a human model of stress-induced hyperalgesia. Pain. 2012; 153(11): 2204-2209.

[25]

Maheandiran M, Mylvaganam S, Wu C, et al. Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality. PLoS One. 2013; 8(12): e83168.

[26]

Antony S, Peeyush Kumar T, Mathew J, Anju TR, Paulose CS. Hypoglycemia induced changes in cholinergic receptor expression in the cerebellum of diabetic rats. J Biomed Sci. 2010; 17(1): 7.

[27]

Shankar K, Gupta D, Mani BK, et al. Ghrelin protects against insulin-induced hypoglycemia in a mouse model of type 1 diabetes mellitus. Front Endocrinol (Lausanne). 2020; 11: 606.

[28]

Ghasemi A, Jeddi S. Streptozotocin as a tool for induction of rat models of diabetes: a practical guide. EXCLI J. 2023; 22: 274-294.

[29]

Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008; 51(2): 216-226.

[30]

Cryer PE. Hypoglycemia in type 1 diabetes mellitus. Endocrinol Metab Clin North Am. 2010; 39(3): 641-654.

[31]

Pasmans K, Meex RCR, van Loon LJC, Blaak EE. Nutritional strategies to attenuate postprandial glycemic response. Obes Rev. 2022; 23(9): e13486.

[32]

Ayala JE, Bracy DP, McGuinness OP, Wasserman DH. Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes. 2006; 55(2): 390-397.

[33]

Cahill GF. Fuel metabolism in starvation. Annu Rev Nutr. 2006; 26: 1-22.

[34]

Kim JK, Fillmore JJ, Chen Y, et al. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A. 2001; 98(13): 7522-7527.

[35]

Burcelin R, Dolci W, Thorens B. Glucose sensing by the hepatoportal sensor is GLUT2-dependent: in vivo analysis in GLUT2-null mice. Diabetes. 2000; 49(10): 1643-1648.

[36]

El Nahas R, Al-Aghbar MA, Herrero L, van Panhuys N, Espino-Guarch M. Applications of genome-editing Technologies for Type 1 diabetes. Int J Mol Sci. 2023; 25(1): 344.

[37]

Al-Awar A, Kupai K, Veszelka M, et al. Experimental Diabetes Mellitus in Different Animal Models. J Diabetes Res. 2016; 2016: 9051426.

[38]

da Silva-Buttkus P, Spielmann N, Klein-Rodewald T, et al. Knockout mouse models as a resource for the study of rare diseases. Mamm Genome. 2023; 34(2): 244-261.

[39]

Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019; 30: 72-130.

[40]

Sabi SH, Alzreqat RK, Almaaytah AM, Masaadeh MM, Abualhaijaa AK. Genetic variations in Hyperinsulinemic hypoglycemia: active versus inactive mutations. Diabetes Metab Syndr Obes. 2024; 17: 4439-4452.

[41]

Demirbilek H, Rahman SA, Buyukyilmaz GG, Hussain K. Diagnosis and treatment of hyperinsulinaemic hypoglycaemia and its implications for paediatric endocrinology. Int J Pediatr Endocrinol. 2017; 2017: 9.

[42]

Butnariu LI, Bizim DA, Păduraru G, et al. Congenital hyperinsulinism caused by mutations in ABCC8 gene associated with early-onset neonatal hypoglycemia: genetic heterogeneity correlated with phenotypic variability. Int J Mol Sci. 2024; 25(10): 5533.

[43]

Sørensen TIA, Metz S, Kilpeläinen TO. Do gene-environment interactions have implications for the precision prevention of type 2 diabetes? Diabetologia. 2022; 65(11): 1804-1813.

[44]

Rosenfeld E, Ganguly A, De Leon DD. Congenital hyperinsulinism disorders: genetic and clinical characteristics. Am J Med Genet C Semin Med Genet. 2019; 181(4): 682-692.

[45]

Dezashibi HM, Shabani A. A mini-review of current treatment approaches and gene therapy as potential interventions for diabetes mellitus types 1. Adv Biomed Res. 2023; 12: 219.

[46]

Tsao DD, Chang KR, Kockel L, Park S, Kim SK. A genetic strategy to measure insulin signaling regulation and physiology in Drosophila. PLoS Genet. 2023; 19(2): e1010619.

[47]

Fabricius TW, Verhulst CEM, Kristensen PL, et al. Hyperinsulinaemic-hypoglycaemic glucose clamps in human research: a systematic review of the literature. Diabetologia. 2021; 64(4): 727-736.

[48]

Owei I, Jain N, Jones D, Umekwe N, Dagogo-Jack S. Physiology of glycemic recovery and stabilization after hyperinsulinemic euglycemic clamp in healthy subjects. J Clin Endocrinol Metab. 2018; 103(11): 4155-4162.

[49]

King AJ. The use of animal models in diabetes research. Br J Pharmacol. 2012; 166(3): 877-894.

[50]

Ghosal S, Nunley A, Mahbod P, et al. Mouse handling limits the impact of stress on metabolic endpoints. Physiol Behav. 2015; 150: 31-37.

[51]

Lee G, Goosens KA. Sampling blood from the lateral tail vein of the rat. J Vis Exp. 2015; 18(99): e52766.

[52]

Mistry S, Gouripeddi R, Reno CM, Abdelrahman S, Fisher SJ, Facelli JC. Detecting hypoglycemia-induced electrocardiogram changes in a rodent model of type 1 diabetes using shape-based clustering. PLoS One. 2023; 18(5): e0284622.

[53]

Floyd B, Chandra P, Hall S, et al. Comparative analysis of the efficacy of continuous glucose monitoring and self-monitoring of blood glucose in type 1 diabetes mellitus. J Diabetes Sci Technol. 2012; 6(5): 1094-1102.

[54]

Manov AE, Chauhan S, Dhillon G, et al. The effectiveness of continuous glucose monitoring devices in managing uncontrolled diabetes mellitus: a retrospective study. Cureus. 2023; 15(7): e42545.

[55]

Rao CH, Liu L, Gao J, Du ZH, Gao C. Establishment of blood glucose control model in diabetic mice. Int J Ophthalmol. 2022; 15(12): 1908-1914.

[56]

Marin N, Moragon A, Gil D, Garcia-Garcia F, Bisbal V. Acclimation and blood sampling: effects on stress markers in C57Bl/6J mice. Animals (Basel). 2023; 13(18): 2816.

[57]

Lyon AW, Lyon ME. Evaluation of precision and bias specifications required to achieve the 2018 FDA guidance criteria for glucose meter performance using simulation models. J Diabetes Sci Technol. 2020; 14(3): 513-518.

[58]

Re M, Del Baldo F, Tardo AM, Fracassi F. Monitoring of diabetes mellitus using the flash glucose monitoring system: the owners' point of view. Vet Sci. 2023; 10(3): 203.

[59]

Byrd MKH, Arneson AG, Soffa DR, Stewart JW, Rhoads ML. Human continuous glucose monitors for measurement of glucose in dairy cows. JDS Commun. 2022; 3(1): 78-83.

[60]

Leelarathna L, English SW, Thabit H, et al. Accuracy of subcutaneous continuous glucose monitoring in critically ill adults: improved sensor performance with enhanced calibrations. Diabetes Technol Ther. 2014; 16(2): 97-101.

[61]

Mihai DA, Stefan DS, Stegaru D, et al. Continuous glucose monitoring devices: a brief presentation (review). Exp Ther Med. 2022; 23(2): 174.

[62]

Arble DM, Ramsey KM, Bass J, Turek FW. Circadian disruption and metabolic disease: findings from animal models. Best Pract Res Clin Endocrinol Metab. 2010; 24(5): 785-800.

[63]

Giridharan NV. Glucose & energy homeostasis: lessons from animal studies. Indian J Med Res. 2018; 148(5): 659-669.

[64]

Soto RJ, Schoenfisch MH. Preclinical performance evaluation of percutaneous glucose biosensors: experimental considerations and recommendations. J Diabetes Sci Technol. 2015; 9(5): 978-984.

[65]

Qian J, Scheer F. Circadian system and glucose metabolism: implications for physiology and disease. Trends Endocrinol Metab. 2016; 27(5): 282-293.

[66]

Deeds MC, Anderson JM, Armstrong AS, et al. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab Anim. 2011; 45(3): 131-140.

[67]

Zhang Y, Sun S, Jia H, et al. The optimized calculation method for insulin dosage in an insulin tolerance test (ITT): a randomized parallel control study. Front Endocrinol (Lausanne). 2020; 11: 202.

[68]

Tomita N, Nakamura T, Sunden Y, Morita T. Histopathological and immunohistochemical analysis of the cerebral white matter after transient hypoglycemia in rat. J Vet Med Sci. 2020; 82(1): 68-76.

[69]

Eddouks M, Chattopadhyay D, Zeggwagh NA. Animal models as tools to investigate antidiabetic and anti-inflammatory plants. Evid Based Complement Alternat Med. 2012; 2012: 142087.

[70]

Fajarwati I, Solihin DD, Wresdiyati T, Batubara I. Administration of alloxan and streptozotocin in Sprague Dawley rats and the challenges in producing diabetes model. IOP Conf Ser Earth Environ Sci. 2023; 1174(1): 012035.

[71]

Tirmenstein M, Horvath J, Graziano M, et al. Utilization of the Zucker diabetic fatty (ZDF) rat model for investigating hypoglycemia-related toxicities. Toxicol Pathol. 2015; 43(6): 825-837.

[72]

MacDonald AJ, Yang YHC, Cruz AM, Beall C, Ellacott KLJ. Brain-body control of glucose homeostasis-insights from model organisms. Front Endocrinol (Lausanne). 2021; 12: 662769.

[73]

Agiostratidou G, Anhalt H, Ball D, et al. Standardizing clinically meaningful outcome measures beyond HbA(1c) for type 1 diabetes: a consensus report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF international, the Leona M. And Harry B. Helmsley Charitable Trust, the pediatric Endocrine Society, and the T1D exchange. Diabetes Care. 2017; 40(12): 1622-1630.

[74]

Benedé-Ubieto R, Estévez-Vázquez O, Ramadori P, Cubero FJ, Nevzorova YA. Guidelines and considerations for metabolic tolerance tests in mice. Diabetes Metab Syndr Obes. 2020; 13: 439-450.

[75]

de Díaz León-Guerrero S, Salazar-León J, Meza-Sosa KF, et al. An enriched environment re-establishes metabolic homeostasis by reducing obesity-induced inflammation. Dis Model Mech. 2022; 15(6): 1-14.

[76]

Gunawan S, Aulia A, Soetikno V. Development of rat metabolic syndrome models: a review. Vet World. 2021; 14(7): 1774-1783.

[77]

Placide E, Arsene M, Parfait K, Irie Bi J, Joseph N, Claude A. Effect of Picralina nitida on the glycemia and intestinal absorption of glucose in rat. GSC Biol Pharm Sci. 2018; 5: 106-114.

[78]

Wediasari F, Nugroho GA, Fadhilah Z, Elya B, Setiawan H, Mozef T. Hypoglycemic effect of a combined Andrographis paniculata and Caesalpinia sappan extract in Streptozocin-induced diabetic rats. Adv Pharmacol Pharm Sci. 2020; 2020: 8856129.

[79]

Quadri S, Prathipati P, Jackson D, Jackson K. Regulation of heme oxygenase-1 induction during recurrent insulin induced hypoglycemia. Int J Med. 2014; 2(2): 47-52.

[80]

Havel PJ, Parry SJ, Stern JS, et al. Redundant parasympathetic and sympathoadrenal mediation of increased glucagon secretion during insulin-induced hypoglycemia in conscious rats. Metabolism. 1994; 43(7): 860-866.

[81]

Moussavi K, Nguyen LT, Hua H, Fitter S. Comparison of IV insulin dosing strategies for hyperkalemia in the emergency department. Critical Care Explorations. 2020; 2(4): e0092.

[82]

Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014; 19(2): 181-192.

[83]

Mastracci TL, Sussel L. The endocrine pancreas: insights into development, differentiation, and diabetes. Wiley Interdiscip Rev Dev Biol. 2012; 1(5): 609-628.

[84]

Irwin N, Francis JM, Flatt PR. Insulin modulates glucose-dependent insulinotropic polypeptide (GIP) secretion from enteroendocrine K cells in rats. Biol Chem. 2011; 392(10): 909-918.

[85]

Demirbilek H, Vuralli D, Haris B, Hussain K. Managing severe Hypoglycaemia in patients with diabetes: current challenges and emerging therapies. Diabetes Metab Syndr Obes. 2023; 16: 259-273.

[86]

McGee D, Chen A, de Garavilla L. Dextrose is absorbed by rectum in hypoglycemic rats. J Emerg Med. 2003; 24(3): 253-257.

[87]

Leclair E, Liggins RT, Peckett AJ, et al. Glucagon responses to exercise-induced hypoglycaemia are improved by somatostatin receptor type 2 antagonism in a rat model of diabetes. Diabetologia. 2016; 59(8): 1724-1731.

[88]

Newman-Lindsay S, Lakshminrusimha S, Sankaran D. Diazoxide for neonatal Hyperinsulinemic hypoglycemia and pulmonary hypertension. Children (Basel). 2022; 10(1): 5.

[89]

Dougherty PP, Klein-Schwartz W. Octreotide's role in the management of sulfonylurea-induced hypoglycemia. J Med Toxicol. 2010; 6(2): 199-206.

[90]

Madar J, Sildan N, Pora EU. Age-dependent rapid antiinsulin effect of hydrocortisone hemisuccinate during insulin induced hypoglycemia in white rat. Ann Endocrinol (Paris). 1975; 36(1): 25-30.

[91]

Takeshi H, Mai O, Takeo Y. Risk of non-hypoglycemic agents for hypoglycemia-related hospitalization in patients with type 2 diabetes: a large-scale medical receipt database analysis. BMJ Open Diabetes Res Care. 2023; 11(2): e003177.

[92]

Ari C, Kovács Z, Juhasz G, et al. Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar albino Glaxo/Rijswijk rats. Front Mol Neurosci. 2017; 9: 137.

[93]

Kesl SL, Poff AM, Ward NP, et al. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Nutr Metab. 2016; 13(1): 9.

[94]

Aitman TJ, Critser JK, Cuppen E, et al. Progress and prospects in rat genetics: a community view. Nat Genet. 2008; 40(5): 516-522.

[95]

De Vos A, Heimberg H, Quartier E, et al. Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression. J Clin Invest. 1995; 96(5): 2489-2495.

[96]

Benner C, van der Meulen T, Cacéres E, Tigyi K, Donaldson CJ, Huising MO. The transcriptional landscape of mouse beta cells compared to human beta cells reveals notable species differences in long non-coding RNA and protein-coding gene expression. BMC Genomics. 2014; 15(1): 620.

[97]

Chandrasekera PC, Pippin JJ. Of rodents and men: species-specific glucose regulation and type 2 diabetes research. ALTEX. 2014; 31(2): 157-176.

[98]

Kowalski GM, Bruce CR. The regulation of glucose metabolism: implications and considerations for the assessment of glucose homeostasis in rodents. Am J Physiol Endocrinol Metab. 2014; 307(10): E859-E871.

[99]

Kleinert M, Clemmensen C, Hofmann SM, et al. Animal models of obesity and diabetes mellitus. Nat Rev Endocrinol. 2018; 14(3): 140-162.

[100]

McNeilly AD, Williamson R, Sutherland C, Balfour DJ, Stewart CA. High fat feeding promotes simultaneous decline in insulin sensitivity and cognitive performance in a delayed matching and non-matching to position task. Behav Brain Res. 2011; 217(1): 134-141.

[101]

Bruss MD, Khambatta CF, Ruby MA, Aggarwal I, Hellerstein MK. Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates. Am J Physiol Endocrinol Metab. 2010; 298(1): E108-E116.

[102]

Sacks DB, Arnold M, Bakris GL, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care. 2011; 34(6): e61-e99.

[103]

Mori H, Okada Y, Kurozumi A, Narisawa M, Tanaka Y. Factors influencing inter-day glycemic variability in diabetic outpatients receiving insulin therapy. J Diabetes Investig. 2017; 8(1): 69-74.

[104]

Frier BM, Ratzki-Leewing A, Harris SB. Reporting of hypoglycaemia in clinical trials of basal insulins: a need for consensus. Diabetes Obes Metab. 2019; 21(7): 1529-1542.

[105]

Brockway R, Tiesma S, Bogie H, et al. Fully implantable arterial blood glucose device for metabolic research applications in rats for two months. J Diabetes Sci Technol. 2015; 9(4): 771-781.

[106]

Fuller KNZ, Thyfault JP. Barriers in translating preclinical rodent exercise metabolism findings to human health. J Appl Physiol. 2021; 130(1): 182-192.

[107]

Tkacs NC, Thompson HJ. From bedside to bench and back again: research issues in animal models of human disease. Biol Res Nurs. 2006; 8(1): 78-88.

[108]

Kumar S, Singh R, Vasudeva N, Sharma S. Acute and chronic animal models for the evaluation of anti-diabetic agents. Cardiovasc Diabetol. 2012; 11: 9.

[109]

Charlès L, Agius T, von Reiterdank IF, et al. Modified tail vein and penile vein puncture for blood Sampling in the rat model. J Vis Exp. 2023; 196: 1-16.

[110]

Nakhleh A, Shehadeh N. Hypoglycemia in diabetes: an update on pathophysiology, treatment, and prevention. World J Diabetes. 2021; 12(12): 2036-2049.

[111]

Cheng Y, Wang H, Li M. The promise of CRISPR/Cas9 technology in diabetes mellitus therapy: how gene editing is revolutionizing diabetes research and treatment. J Diabetes Complications. 2023; 37(8): 108524.

[112]

Boti MA, Athanasopoulou K, Adamopoulos PG, Sideris DC, Scorilas A. Recent advances in genome-engineering strategies. Genes (Basel). 2023; 14(1): 129.

[113]

Bevacqua RJ, Dai X, Lam JY, et al. CRISPR-based genome editing in primary human pancreatic islet cells. Nat Commun. 2021; 12(1): 2397.

[114]

Vaddiraju S, Burgess DJ, Tomazos I, Jain FC, Papadimitrakopoulos F. Technologies for continuous glucose monitoring: current problems and future promises. J Diabetes Sci Technol. 2010; 4(6): 1540-1562.

[115]

Hermanns N, Heinemann L, Freckmann G, Waldenmaier D, Ehrmann D. Impact of CGM on the management of hypoglycemia problems: overview and secondary analysis of the HypoDE study. J Diabetes Sci Technol. 2019; 13(4): 636-644.

[116]

Rooijackers HM, Wiegers EC, Tack CJ, van der Graaf M, de Galan BE. Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies. Cell Mol Life Sci. 2016; 73(4): 705-722.

[117]

Clemente-Suárez VJ, Martín-Rodríguez A, Redondo-Flórez L, López-Mora C, Yáñez-Sepúlveda R, Tornero-Aguilera JF. New insights and potential therapeutic interventions in metabolic diseases. Int J Mol Sci. 2023; 24(13): 10672.

[118]

Kim SW, Choi JW, Yun JW, et al. Proteomics approach to identify serum biomarkers associated with the progression of diabetes in Korean patients with abdominal obesity. PLoS One. 2019; 14(9): e0222032.

[119]

Bathla G, Policeni B, Agarwal A. Neuroimaging in patients with abnormal blood glucose levels. AJNR Am J Neuroradiol. 2014; 35(5): 833-840.

[120]

Akhaury K, Wanjari A, Sinha AH, Kumar M. Hypoglycemia and cardiovascular disease: exploring the connections. Cureus. 2023; 15(10): e47784.

[121]

Rogal J, Zbinden A, Schenke-Layland K, Loskill P. Stem-cell based organ-on-a-chip models for diabetes research. Adv Drug Deliv Rev. 2019; 140: 101-128.

[122]

Rodríguez-Comas J, Ramón-Azcón J. Islet-on-a-chip for the study of pancreatic β-cell function. In Vitro Models. 2022; 1(1): 41-57.

[123]

Shroff T, Aina K, Maass C, et al. Studying metabolism with multi-organ chips: new tools for disease modelling, pharmacokinetics and pharmacodynamics. Open Biol. 2022; 12(3): 210333.

[124]

Mou L, Mandal K, Mecwan M, et al. Integrated biosensors for monitoring microphysiological systems. Lab Chip. 2022; 22: 3801-3816.

[125]

Lithovius V, Otonkoski T. Stem cell based models in congenital Hyperinsulinism - perspective on practicalities and possibilities. Front Endocrinol (Lausanne). 2022; 13: 837450.

[126]

Hu C, Jia W. Multi-omics profiling: the way towards precision medicine in metabolic diseases. J Mol Cell Biol. 2021; 13(8): 576-593.

[127]

Castillo-Armengol J, Marzetta F, Rodriguez Sanchez-Archidona A, et al. Disrupted hypothalamic transcriptomics and proteomics in a mouse model of type 2 diabetes exposed to recurrent hypoglycaemia. Diabetologia. 2024; 67(2): 371-391.

[128]

Dilworth L, Facey A, Omoruyi F. Diabetes mellitus and its metabolic complications: the role of adipose tissues. Int J Mol Sci. 2021; 22(14): 7644.

[129]

González P, Lozano P, Ros G, Solano F. Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections. Int J Mol Sci. 2023; 24(11): 9352.

RIGHTS & PERMISSIONS

2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

AI Summary AI Mindmap
PDF

24

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/