Download PDF
CC BY-NC-ND 4.0 · Ann Natl Acad Med Sci 2018; 54(02): 064-073
DOI: 10.1055/s-0040-1712788
Mini Review

Glucose - Responsive Smart Insulin

Aishwarya Krishnamurthy
Department of Endocrinology and Metabolism All India Institute of Medical Sciences, New Delhi.
,
Ravinder Goswami
Department of Endocrinology and Metabolism All India Institute of Medical Sciences, New Delhi.
› Author Affiliations
› Further Information
  PDF Download Permissions and Reprints

ABSTRACT

The discovery of insulin in 1920s revolutionized the management of Type 1 Diabetes Mellitus. The evolution of insulin over the last nine decades has seen three phases, namely discovery and understanding of the molecule, advances in synthesis of the molecule and advancements in the optimization of insulin structure and delivery. These advances aim to minimize hypoglycemia while simultaneously improving anti-hyperglycemic efficacy. Glucose-responsive insulin (GRI) systems were first conceptualized in 1979. These are novel insulin formulations that provide anti hyperglycemic activity appropriate to circulating glucose levels but with a mechanism to avoid hypoglycemia, that often accompanies stringent glycemic control. GRIs are of three major typesalgorithm-based mechanical, polymer-based, molecular GRI analog systems. They differ in the mechanisms of achieving glucose responsiveness. Algorithm-based systems are closed loop insulin pumps that adjust insulin delivery commensurate with blood glucose levels on the basis of predetermined algorithms, that terminate or increase insulin delivery according to blood glucose trends. The second category of GRI includes glucose-responsive polymer-based matrices that house insulin, releasing insulin as needed based on ambient glucose levels. The third approach is to incorporate glucose sensitive motifs in the insulin molecule itself that would decrease or increase insulin availability based on blood glucose levels. The mechanisms behind these novel approaches to insulin delivery and action will be the focus of this review article.



Publication History

Article published online:
08 May 2020

© .

Thieme Medical and Scientific publishers private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 

  • References

  • 1 Laguesse E (1893). Sur la formation des ilots de Langerhans dans le pancréas. ComptesRendusHebdomadaires des séances et memoires de la société de biologie 5: 819-820.
  • 2 Von Mering J, Minkowski O (1890). Diabetes mellitus nach pankreasexstirpation. Archiv Exp pathol pharmakol 26: 371-387.
  • 3 Karamistos DT (2011). The story of insulin discovery. Diabetes Res Clin pract 93 (Suppl 1): S2-S8.
  • 4 Mayer Jp, Zhang F, DiMarchi RD (2007). Insulin structure and function. Biopolymers 88: 687-713.
  • 5 Sanger F, Tuppy H (1951). The amino-acid sequence in the phenylalanyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates. Biochem J 49: 481-490.
  • 6 Goeddel DV, Kleid DG, Bolivar F, et al (1979). Expression in Escherichia coli of chemically synthesized genes for human insulin. proc Natl Acad Sci USA 76: 106-110.
  • 7 Zaykov AN, Mayer Jp, DiMarchi RD (2016). pursuit of a perfect insulin. Nat Rev Drug Discov 15: 425-439.
  • 8 Rege NK, phillips NFB, Weiss MA (2017). Development of Glucose-Responsive “Smart” Insulin Systems. Curr Opin Endocrinol Diabetes Obes 24(4): 267-278.
  • 9 Halvorson M, Carpenter S, Kaiserman K, Kaufman FR (2007). A pilot trial in pediatrics with the sensor-augmented pump: combining real-time continuous glucose monitoring with the insulin pump. J pediatr 150: 103-105.
  • 10 Saltiel AR, pessin JE (2002). Insulin signaling pathways in time and space. Trends Cell Biol 12: 65-71.
  • 11 Ravaine V, Ancla C, Catargi B (2008). Chemically controlled closed-loop insulin delivery. J Contr Rel 132: 2-11.
  • 12 Hoeg-Jensen T, Ridderberg S, Havelund S, et al (2005). Insulins with built-in glucose sensors for glucose responsive insulin release. J pept Sci 11: 339-346.
  • 13 Breton M, Farret A, Bruttomesso D, et al (2012). Fully integrated artificial pancreas in type 1 diabetes: modular closed-loop glucose control maintains near normoglycemia. Diabetes 61: 2230-2237.
  • 14 Ly TT, Roy A, Grosman B, et al (2015). Day and night closed-loop control using the integrated medtronic hybrid closed-loop system in type 1 diabetes at diabetes camp. Diabetes Care 38: 1205-1211.
  • 15 Doyle FJ, Huyett LM, Lee JB, et al (2014). Closed-loop artificial pancreas systems: engineering the algorithms. Diabetes Care 37: 1191-1197.
  • 16 pinsker JE, Lee JB, Dassau E, et al (2016). Randomized crossover comparison of personalized MpC and pID control algorithms for the artificial pancreas. Diabetes Care 39: 1135-1142.
  • 17 Blauw H, Keith-Hynes p, Koops R, DeVries JH (2016). A review of safety and design requirements of the artificial pancreas. Ann Biomed Eng 44:3158-3172.
  • 18 El-Khatib FH, Balliro C, Hillard MA, et al (2016). Home use of a bihormonal bionic pancreas versus insulin pump therapy inadults with type 1 diabetes: a multicentrerandomised crossover trial. Lancet 389: 369-380.
  • 19 Schade DS, Eaton Rp, Friedman JE, Spencer WJ (1980). Normalization of plasma insulin profiles with intraperitoneal insulin in diabetic man. Diabetologia 19: 35-39.
  • 20 Schade DS, Eaton p (1980). The peritoneum—a potential insulin delivery route for a mechanical pancreas. Diabetes Care 3: 229-234.
  • 21 podual K, Doyle F, peppas NA (2004). Modeling of water transport in and release from glucose-sensitive swelling-controlled release systems based on poly (diethylaminoethyl methacrylate-gethylene glycol). Ind Eng Chem Res 43: 7500-7512.
  • 22 Lee YM, Kim SH, Cho CS (1996). Synthesis and swelling characteristics of pH and thermoresponsive interpenetrating polymer network hydrogel composed of poly (vinyl alcohol) and poly (acrylic acid). J Appl polym Sci 62: 301-311.
  • 23 Kitano S, Koyama Y, Kataoka K, et al (1992). A novel drug delivery system utilizing a glucose responsive polymer complex between poly (vinyl alcohol) and poly (N-vinyl-2-pyrrolidone) with a phenylboronic acid moiety. J Controlled Rel 19: 161-170.
  • 24 Li X, Fu M, Wu J, et al (2017). pH-sensitive peptide hydrogel for glucose-responsive insulin delivery. Acta Biomater 51: 294-303.
  • 25 Anirudhan T, Nair AS, Nair SS (2016). Enzyme coated beta-cyclodextrin for effective adsorption and glucose-responsive closed-loop insulin delivery. Int J BiolMacromol 91: 818-827.
  • 26 Brownlee M, Cerami A (1979). A glucose-controlled insulin-delivery system: semisynthetic insulin bound to lectin. Science 206: 1190-1191.
  • 27 Drickamer K, Taylor ME (1993). Biology of animal lectins. Ann Rev Cell Biol 9: 237-264.
  • 28 Ballerstadt R, Evans C, McNichols R, Gowda A (2006). Concanavalin A for in Glucose - Responsive Smart Insulin 73 vivo glucose sensing: a biotoxicity review. Biosens Bioelectron 22: 275-284.
  • 29 Xie S, Li Z, Yu Z (2015). Microneedles for transdermal delivery of insulin. J Drug Deliv Sci Technol 28: 11-17.
  • 30 Ye Y, Yu J, Wang C, et al (2016). Microneedles integrated with pancreatic cells and synthetic glucose-signal amplifiers for smart insulin delivery. Adv Mater 28(16): 3115-3121.
  • 31 Hilgenfeld R, Seipke G, Berchtold H, et al (2014). The evolution of insulin glargine and its continuing contribution to diabetes care. Drugs 74: 911-927.
  • 32 Ito Y, Imanishi Y (1994). protein device for glucose-sensitive release of insulin. polymeric Drugs Drug Administr 1994: 47-54.
  • 33 Kashyap N, pohl R, Bruen K, Leone E, Steiner S, eds. (2010). 'Smart' basal insulin formulation that releases insulin in response to blood glucose concentrations of diabetic swine. Abstracts of Annual Meeting of Controlled Release Society. portland, OR: Controlled Release Society.
  • 34 Chou DH, Webber MJ, Tang BC, et al (2015). Glucose-responsive insulin activity by covalent modification with aliphatic phenylboronic acid conjugates. proc Natl Acad Sci USA 112: 2401-2406.
  • 35 Zion TC, Lancaster TL (2010). Conjugate based systems for controlled drug delivery. patent application WO2010088294 A1. 5 August 2010.
  • 36 Kaarsholm NC, Lin S, Yan L, et al (2018). Engineering glucose responsiveness into insulin. Diabetes 67(2):299-308.