Citation: Li-Dan Hu, Yu-Lin Zhang, Hong Wang, Xing-Yue Peng, Yi Wang. Highly efficient detection of insulinotropic action of glucagon via GLP-1 receptor in mice pancreatic beta-cell with a novel perfusion microchip[J]. Chinese Chemical Letters, ;2016, 27(7): 1027-1031. doi: 10.1016/j.cclet.2016.05.023 shu

Highly efficient detection of insulinotropic action of glucagon via GLP-1 receptor in mice pancreatic beta-cell with a novel perfusion microchip

a.
School of Life Sciences, Xiamen University, Xiamen 361005, China
b.
Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China
c.
College of Life Sciences and Technology, Huazhong University of Science and Technology, Wuhan 430074, China

Corresponding author: Yi Wang, wangyideyouxiang@sohu.com
Received Date: 28 April 2016
Revised Date: 18 May 2016
Accepted Date: 24 May 2016
Available Online: 1 July 2016

Figures(4)

Glucagon exhibits insulinotropic ability by activating cAMP through glucagon or glucagon-like peptide-1 (GLP-1) receptors. To investigate the mechanism of endogenous and exogenous glucagon on insulin release, we studied the receptor selectivity on pancreatic islet beta-cells by switching the glucose concentration from 20 mmol/L to 0 mmol/L. To measure the exact temporal relationship between glucagon and insulin release, we developed a quick, small volume, multi-channel polydimethylsiloxane (PDMS) microchip. At 0 mmol/L glucose, we observed an insulinotropic effect in both INS-1 cells and islets. Meanwhile, we observed a 63 ± 6.27 s delay of endogenous glucagon-induced insulin release. After treatment with glucagon and GLP-1 receptor antagonists, we found that endogenous glucagon utilized the glucagon receptor, whereas exogenous glucagon primarily utilized the GLP-1 receptor to promote insulin secretion. The microchip can also be used to describe the “glucagonocentric” vision of diabetes pathophysiology. Taken together, the insulinotropic mechanism of different receptors should be taken into account in clinical treatments.
- Glucagon,
- Insulin,
- Glucagon receptor,
- GLP-1 receptor,
- Microchip
1. [1]
  E.W. Sutherland, C. De Duve. Origin and distribution of the hyperglycemicglycogenolytic factor of the pancreas[J]. J. Biol. Chem., 1948,175:663-674.
2. [2]
  R.H. Unger, A.D. Cherrington. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover[J]. J. Clin. Invest., 2012,122:4-12. doi: 10.1172/JCI60016
3. [3]
  B.E. Dunning, J.E. Gerich. The role of a-cell dysregulation in fasting and postprandial hyperglycemia in type, 2 diabetes and therapeutic implications[J]. Endocr. Rev., 2007,28:253-283. doi: 10.1210/er.2006-0026
4. [4]
  Y. Lee, E.D. Berglund, X.X. Yu. Hyperglycemia in rodent models of type, 2 diabetes requires insulin-resistant alpha cells[J]. Proc. Natl. Acad. Sci. U. S. A., 2014,111:13217-13222. doi: 10.1073/pnas.1409638111
5. [5]
  R.H. Unger, L. Orci. The essential role of glucagon in the pathogenesis of diabetes mellitus[J]. Lancet, 1975,305:14-16. doi: 10.1016/S0140-6736(75)92375-2
6. [6]
  A.D. Baron, L. Schaeffer, P. Shragg, O.G. Kolterman. Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics[J]. Diabetes, 1987,36:274-283. doi: 10.2337/diab.36.3.274
7. [7]
  H.Y. Gaisano, P.E. Macdonald, M. Vranic. Glucagon secretion and signaling in the development of diabetes[J]. Front. Physiol., 2012,3349.
8. [8]
  S. Malmgren, B. Ahré n. Evidence for time dependent variation of glucagon secretion in mice[J]. Peptides, 2016,76:102-107. doi: 10.1016/j.peptides.2016.01.008
9. [9]
  L.R. Nyman, K.S. Wells, W.S. Head. Real-time, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets[J]. J. Clin. Invest., 2008,118:3790-3797. doi: 10.1172/JCI36209
10. [10]
  E. Samols, G. Marri, V. Marks. Interrelationship of glucagon, insulin and glucose: the insulinogenic effect of glucagon[J]. Diabetes, 1966,15:855-866. doi: 10.2337/diab.15.12.855
11. [11]
  P. Huypens, Z. Ling, D. Pipeleers, F. Schuit. Glucagon receptors on human islet cells contribute to glucose competence of insulin release[J]. Diabetologia, 2000,43:1012-1019. doi: 10.1007/s001250051484
12. [12]
  K. Moens, D. Flamez, C. Van Schravendijk. Dual glucagon recognition by pancreatic β-cells via glucagon and glucagon-like peptide, 1 receptors[J]. Diabetes, 1998,47:66-72. doi: 10.2337/diab.47.1.66
13. [13]
  J.S. Mohammed, Y. Wang, T.A. Harvat, J. Oberholzer, D.T. Eddington. Microfluidic device for multimodal characterization of pancreatic islets[J]. Lab Chip, 2009,9:97-106. doi: 10.1039/B809590F
14. [14]
  S. Runge, B.S. Wulff, K. Madsen, H. Bräuner-Osborne, L.B. Knudsen. Different domains of the glucagon and glucagon-like peptide-1 receptors provide the critical determinants of ligand selectivity[J]. Br. J. Pharmacol., 2003,138:787-794. doi: 10.1038/sj.bjp.0705120
15. [15]
  L.J. Jelinek, S. Lok, G.B. Rosenberg. Expression cloning and signaling properties of the rat glucagon receptor[J]. Science, 1993,259:1614-1616. doi: 10.1126/science.8384375
16. [16]
  L.B. Knudsen, D. Kiel, M. Teng. Small-molecule agonists for the glucagon-like peptide, 1 receptor[J]. Proc. Natl. Acad. Sci. U. S. A., 2007,104:937-942. doi: 10.1073/pnas.0605701104
17. [17]
  D.J. Drucker, J. Philippe, S. Mojsov, W.L. Chick, J.F. Habener. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line[J]. Proc. Natl. Acad. Sci. U. S. A., 1987,84:3434-3438. doi: 10.1073/pnas.84.10.3434
18. [18]
  B. Portha, C. Tourrel-Cuzin, J. Movassat. Activation of the GLP-1 receptor signalling pathway: a relevant strategy to repair a deficient beta-cell mass[J]. Exp. Diabetes Res., 2011,2011376509.
19. [19]
  P.E. MacDonald, W. El-Kholy, M.J. Riedel. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion[J]. Diabetes, 2002,51:S434-S442. doi: 10.2337/diabetes.51.2007.S434
20. [20]
  K.M. Hope, P.O.T. Tran, H.R. Zhou. Regulation of α-cell function by the β-cell in isolated human and rat islets deprived of glucose: the “switch-off” hypothesis[J]. Diabetes, 2004,53:1488-1495. doi: 10.2337/diabetes.53.6.1488
21. [21]
  G. Tian, S. Sandler, E. Gylfe, A. Tengholm. Glucose- and hormone-induced cAMP oscillations in α- and β-cells within intact pancreatic islets[J]. Diabetes, 2011,60:1535-1543. doi: 10.2337/db10-1087
22. [22]
  L.R. Landa Jr., M. Harbeck, K. Kaihara. Interplay of Ca²⁺ and cAMP signaling in the insulin-secreting MIN6 b-cell line[J]. J. Biol. Chem., 2005,280:31294-31302. doi: 10.1074/jbc.M505657200
23. [23]
  B. Hellman, A. Salehi, E. Grapengiesser, E. Gylfe. Isolated mouse islets respond to glucose with an initial peak of glucagon release followed by pulses of insulin and somatostatin in antisynchrony with glucagon[J]. Biochem. Biophys. Res. Commun., 2012,417:1219-1223. doi: 10.1016/j.bbrc.2011.12.113
24. [24]
  H. Yoowarren, A.G. Willse, N. Hancock. Regulation of rat glucagon receptor expression[J]. Biochem. Biophys. Res. Commun., 1994,205:347-353. doi: 10.1006/bbrc.1994.2671
25. [25]
  N. Abrahamsen, E. Nishimura. Regulation of glucagon and glucagon-like peptide-1 receptor messenger ribonucleic acid expression in cultured rat pancreatic islets by glucose, cyclic adenosine, 30, 50-monophosphate, and glucocorticoids[J]. Endocrinology, 1995,136:1572-1578.
26. [26]
  G. Xu, H. Kaneto, D.R. Laybutt. Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes[J]. Diabetes, 2007,56:1551-1558. doi: 10.2337/db06-1033
27. [27]
  A.P. van Beek, E.R. de Haas, W.A. van Vloten. The glucagonoma syndrome and necrolytic migratory erythema: a clinical review[J]. Eur. J. Endocrinol., 2004,151:531-537. doi: 10.1530/eje.0.1510531
1. [1]
  Lu Li , Suticha Chunta , Xianzi Zheng , Haisheng He , Wei Wu , Yi Lu . β-Lactoglobulin stabilized lipid nanoparticles enhance oral absorption of insulin by slowing down lipolysis. Chinese Chemical Letters, 2024, 35(4): 108662-. doi: 10.1016/j.cclet.2023.108662
2. [2]
  Zhibin Ren , Shan Li , Xiaoying Liu , Guanghao Lv , Lei Chen , Jingli Wang , Xingyi Li , Jiaqing Wang . Penetrating efficiency of supramolecular hydrogel eye drops: Electrostatic interaction surpasses ligand-receptor interaction. Chinese Chemical Letters, 2024, 35(11): 109629-. doi: 10.1016/j.cclet.2024.109629
3. [3]
  Kai Wang , Yun Wang , Lihang Wang , Zhuhai Li , Xi Yu , Xuanhe You , Diwei Wu , Yueming Song , Jiancheng Zeng , Zongke Zhou , Shishu Huang , Yunfeng Lin . Therapeutic siRNA targeting CC chemokine receptor 2 loaded with tetrahedral framework nucleic acid alleviates neuropathic pain by regulating microglial polarization. Chinese Chemical Letters, 2025, 36(3): 109868-. doi: 10.1016/j.cclet.2024.109868
4. [4]
  Qin Yu , Haisheng He , Jianping Qi , Yi Lu , Wei Wu . Oral delivery of insulin by barbed microneedles actuated by intestinal peristalsis. Chinese Chemical Letters, 2024, 35(9): 109888-. doi: 10.1016/j.cclet.2024.109888
5. [5]
  Wangyan Hu , Ke Li , Xiangnan Dou , Ning Li , Xiayan Wang . Nano-sized stationary phase packings retained by single-particle frit for microchip liquid chromatography. Chinese Chemical Letters, 2024, 35(4): 108806-. doi: 10.1016/j.cclet.2023.108806
6. [6]
  Wujun Jian , Mong-Feng Chiou , Yajun Li , Hongli Bao , Song Yang . Cu-catalyzed regioselective diborylation of 1,3-enynes for the efficient synthesis of 1,4-diborylated allenes. Chinese Chemical Letters, 2024, 35(5): 108980-. doi: 10.1016/j.cclet.2023.108980
7. [7]
  Chunhua Ma , Mengjiao Liu , Siyu Ouyang , Zhenwei Cui , Jingjing Bi , Yuqin Jiang , Zhiguo Zhang . Metal-free construction of diverse 1,2,4-triazolo[1,5-a]pyridines on water. Chinese Chemical Letters, 2025, 36(1): 109755-. doi: 10.1016/j.cclet.2024.109755
8. [8]
  Liangfeng Yang , Liang Zeng , Yanping Zhu , Qiuan Wang , Jinheng Li . Copper-catalyzed photoredox 1,4-amidocyanation of 1,3-enynes with N-amidopyridin-1-ium salts and TMSCN: Facile access to α-amido allenyl nitriles. Chinese Chemical Letters, 2024, 35(11): 109685-. doi: 10.1016/j.cclet.2024.109685
9. [9]
  . 第41卷第1期封面和目次. Acta Physico-Chimica Sinica, 2025, 41(1): -.
10. [10]
  Huiju Cao , Lei Shi . sp¹-Hybridized linear and cyclic carbon chain. Chinese Chemical Letters, 2025, 36(4): 110466-. doi: 10.1016/j.cclet.2024.110466
11. [11]
  Gaofeng WANG , Shuwen SUN , Yanfei ZHAO , Lixin MENG , Bohui WEI . Structural diversity and luminescence properties of three zinc coordination polymers based on bis(4-(1H-imidazol-1-yl)phenyl)methanone. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 849-856. doi: 10.11862/CJIC.20230479
12. [12]
  Hai-Yang Song , Jun Jiang , Yu-Hang Song , Min-Hang Zhou , Chao Wu , Xiang Chen , Wei-Min He . Supporting-electrolyte-free electrochemical [2 + 2 + 1] annulation of benzo[d]isothiazole 1,1-dioxides, N-arylglycines and paraformaldehyde. Chinese Chemical Letters, 2024, 35(6): 109246-. doi: 10.1016/j.cclet.2023.109246
13. [13]
  Zhiwei Chen , Heyun Sheng , Xue Li , Menghan Chen , Xin Li , Qiuling Song . Efficient capture of difluorocarbene by pyridinium 1,4-zwitterionic thiolates: A concise synthesis of difluoromethylene-containing 1,4-thiazine derivatives. Chinese Chemical Letters, 2024, 35(4): 108937-. doi: 10.1016/j.cclet.2023.108937
14. [14]
  Jinge Zhu , Ailing Tang , Leyi Tang , Peiqing Cong , Chao Li , Qing Guo , Zongtao Wang , Xiaoru Xu , Jiang Wu , Erjun Zhou . Chlorination of benzyl group on the terminal unit of A₂-A₁-D-A₁-A₂ type nonfullerene acceptor for high-voltage organic solar cells. Chinese Chemical Letters, 2025, 36(1): 110233-. doi: 10.1016/j.cclet.2024.110233
15. [15]
  Qi Li , Zi-Lu Wang , Yun-He Xu . Copper-catalyzed 1,4-silylcyanation of 1,3-enynes: A silyl radical-initiated approach for synthesis of difunctionalized allenes. Chinese Chemical Letters, 2025, 36(3): 109991-. doi: 10.1016/j.cclet.2024.109991
16. [16]
  Peiyan Zhu , Yanyan Yang , Hui Li , Jinhua Wang , Shiqing Li . Rh(Ⅲ)‐Catalyzed sequential ring‐retentive/‐opening [4 + 2] annulations of 2H‐imidazoles towards full‐color emissive imidazo[5,1‐a]isoquinolinium salts and AIE‐active non‐symmetric 1,1′‐biisoquinolines. Chinese Chemical Letters, 2024, 35(10): 109533-. doi: 10.1016/j.cclet.2024.109533
17. [17]
  Junjun Huang , Ran Chen , Yajian Huang , Hang Zhang , Anran Zheng , Qing Xiao , Dan Wu , Ruxia Duan , Zhi Zhou , Fei He , Wei Yi . Discovery of an enantiopure N-[2-hydroxy-3-phenyl piperazine propyl]-aromatic carboxamide derivative as highly selective α_1D/1A-adrenoceptor antagonist and homology modelling. Chinese Chemical Letters, 2024, 35(11): 109594-. doi: 10.1016/j.cclet.2024.109594
18. [18]
  Haitao Yin , Liang Meng , Li Li , Jiamu Xiao , Longrui Liang , Nannan Huang , Yansong Shi , Angang Zhao , Jingwen Hou . Polydopamine-modified biochar supported polylactic acid and zero-valent iron affects the functional microbial community structure for 1,1,1-trichloroethane removal in simulated groundwater. Chinese Chemical Letters, 2025, 36(1): 110313-. doi: 10.1016/j.cclet.2024.110313
19. [19]
  Jiayu Huang , Kuan Chang , Qi Liu , Yameng Xie , Zhijia Song , Zhiping Zheng , Qin Kuang . Fe-N-C nanostick derived from 1D Fe-ZIFs for Electrocatalytic oxygen reduction. Chinese Journal of Structural Chemistry, 2023, 42(10): 100097-100097. doi: 10.1016/j.cjsc.2023.100097
20. [20]
  Jun Xiong , Ke-Ke Chen , Neng-Bin Xie , Wei Chen , Wen-Xuan Shao , Tong-Tong Ji , Si-Yu Yu , Yu-Qi Feng , Bi-Feng Yuan . Demethylase-assisted site-specific detection of N¹-methyladenosine in RNA. Chinese Chemical Letters, 2024, 35(5): 108953-. doi: 10.1016/j.cclet.2023.108953

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(732)
HTML views(5)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142