Main Article Content

Dudi Hardianto


Diabetes mellitus (DM) is a metabolic disorder disease characterized by hyperglycemia due to insulin deficiency, insulin resistance, or both. In 2019, people with DM reached 463 million in the world and will increase to 700 million by 2045. The total global health costs for DM treatment reach the US $760 billion. This review aims to explain the production, types, analysis, and route of insulin delivery. Human insulin is the first recombinant protein produced using genetic engineering. Escherichia coli, Saccharomyces cerevisiae, and Pichia pastoris are commonly host cells for producing human insulin and analogues. Currently, human insulin and analogues have replaced insulin derived from animal pancreas extracts. Analysis of insulin can be carried out through immunoassays, chromatography, and electrochemical biosensors. The route of delivery of insulin can be through subcutaneous injection, nasal, oral, and transdermal. Insulin is the primary drug in patients with type 1 diabetes mellitus (T1DM). In some cases, type 2 diabetes mellitus (T2DM) requires insulin for its treatment. The development of insulin delivery routes will improve compliance, convenience, and treatment effectiveness for DM patients.

Diabetes melitus (DM) merupakan penyakit kelainan metabolisme yang ditandai dengan hiperglikemia karena kekurangan insulin, resistensi insulin, atau keduanya. Pada tahun 2019, penderita DM mencapai 463 juta di dunia dan akan meningkat menjadi 700 juta pada tahun 2045. Total biaya Kesehatan global untuk penanganan DM mencapai US $760 miliar. Telaah ini bertujuan untuk menjelaskan tentang produksi, jenis, analisis, dan rute pemberian insulin. Insulin manusia merupakan protein rekombinan yang pertama diproduksi menggunakan rekayasa genetika. Escherichia coli, Saccharomyces cerevisiae, dan Pichia pastoris merupakan sel inang yang umum digunakan untuk memproduksi insulin manusia dan insulin analog. Saat ini, insulin manusia dan insulin analog telah menggantikan insulin yang berasal dari ekstrak pankreas hewan. Analisis insulin dapat menggunakan immunoassay, kromatografi, dan biosensor elektrokimia. Rute pemberian insulin dapat melalui injeksi subkutan, nasal, oral, dan transdermal. Insulin digunakan sebagai obat utama pada penderita diabetes melitus tipe 1 (DMT1). Dalam beberapa kasus, diabetes melitus tipe 2 (DMT2) memerlukan insulin untuk pengobatannya. Pengembangan rute pemberian insulin akan meningkatkan kepatuhan penderita DM dan efektivitas pengobatan.

Article Details

How to Cite
Hardianto, D. (2021). INSULIN: PRODUKSI, JENIS, ANALISIS, DAN RUTE PEMBERIAN. Jurnal Bioteknologi &Amp; Biosains Indonesia (JBBI), 8(2), 321–331.
Review Article
Author Biography

Dudi Hardianto, Badan Riset dan Inovasi Nasional, Gedung LAPTIAB 610-612, Kawasan Puspiptek Tangerang Selatan, Banten 15314


Academic Profile:

JBBI Reviewer: Hardianto

Research Gate: Hardianto

IPI Portal Garuda: Hardianto


Ahad A, M Raish, YAB Jardin, AM Al-Mohizea, FI Al-Jenoobi (2021) Delivery of insulin via skin route for the management of diabetes mellitus: approach for breaching the obstacles. Pharmaceutics, 13(100):1-17. doi:

Ahmad K (2014) Insulin sources and types: a review of insulin in terms of its mode on diabetes mellitus. J Tradit Chin Med, 34(2): 234-237. Accessed 27 May 2021.

Allen D, C Ruan, B king, K Ruan (2019) Recent advances and near future of insulin pro-duction and therapy. Future Med Chem, 11(13): 1513-1517. doi:

Alkhatib AJ, AM Sindiani, EH Alshdaifat (2021) Insulin as a predictor of diabetes type 2: a new medical hypothesis. Adv Obes Weight Manag Control, 11(1): 1-3. doi: 10.15406/aowmc.2021.11.00328

Baeshen NA, MN Baeshen, A Sheikh, RS Bora, MMM Ahmed, HAI Ramadan, KS Saini, EM Redwan (2014) Cell factories for insulin production Microb Cell Factories, 13(141): 1-9. doi: 10.1186/s12934-014-0141-0

Baruah MP (2011) Insulin pens: the modern delivery devices. J Assoc Physicians India, 59:38-40. Accessed 31 May 2021.

Benyettou F, N Kaddour, T Prakasam, G Das, SK Sharma, SA Thomas, F Bekheti-Sari, J Whelan, MA Alkhalifah, M Khair, H Traboulsi, R Pasricha, R Jagannathan, NM Soulimae, F Gandara, A Trabolsi (2021) In vivo oral insulin delivery via covalent or-ganic frameworks. Chem Sci, 12: 6037-6047. doi: 10.1039/d0sc05328g

Beran D, RO Laing, W Kaplan, R Knox, A Sharma, VJ Wirtz, J Frye, M Ewen (2019) A perspective on global access to insulin: a descriptive study of the market, trade flows and prices. Diabetic Med, 36: 726-733. doi: 10.1111/dme.13947

Cheng AYY, DK Patel, TS Reid, K Wyne (2019) Differentiating basal insulin prepara-tions: understanding how they work explains why they are different. Adv Ther, 36: 1018-1030. doi:

Davidson MB (2015) Insulin therapy: a personal approach. Clin Diabetes J, 33(3): 123-134. doi: 10.2337/diaclin.33.3.123

Demir T, S Turan, K Unluhizarci, O Topaloglu, T Tukek, DG Yavuz (2021) Use of insulin degludec/insulin aspart in the management of diabetes mellitus: expert panel rec-ommendation on appropriate practice patterns. Frontiers Endocrinol, 12: 1-11. doi: 10.3389/fendo.2021.616514

Fonte P, F Araujo, S Reis, B Sarmento (2013) Oral insulin delivery: how far are we? J Diabetes Sci Technol, 7(2): 520-531. doi: 10.1177/193229681300700228

Ghosh S, R Ghosh (2020) Glargine-300: an updated literature review on randomized controlled trials and real-world studies. World J Diabetes, 11(4): 100-114. doi: 10.4239/wjd.v11.i4.100

Gorska-Ciebiada M, M Masierek, M Ciebiada (2020) Improved insulin injection tech-nique, treatment satisfaction and glycemic control: result from a large cohort edu-cation study. J Clin Translational Endocrinol, 19(100217): 1-6. doi:

Gotham D, MJ Barber, A Hill (2018) Production costs and potential prices for biosimilars of human insulin and insulin analogues. BMJ Glo Health,1-10. doi: 10.1136/bmjgh-2018-000850

Govender K, T Naicker, J Lin, S Baijnath, AA Chuturgoon, NS Abdul, T Docrat, HG Kru-ger, T Govender (2020) A novel and more efficient biosynthesis approach from human insulin production in Escherichia coli (E. coli). AMB Express 10(43): 1-9. doi:

Hardianto D (2020) Telaah komprehensif diabetes melitus: klasifikasi, gejala, diagnosis, pecegahan, dan pengobatan. J Bioteknol Biosains Indones, 7(2): 304-317. doi:

Heise T (2021) The future of insulin therapy. Diabetes Res Clin Pract, 175: 1-9. doi:

Hirsch IB, R Juneja, JM Beals, CJ Antalis, EE Wright (2020) The evolution of insulin and how it informs therapy and treatment choices. Endocrin Rev, 41(5): 733-755. doi: 10.1210/endrev/bnaa015

Home P (2021) The evolution of insulin therapy. Diabetes Res Clin Practice 175(108816):1-8. doi:

Jacob S, MA Morsy, A Nair (2018) An overview on the insulin preparation and devices. Indian J Pharma Edu Res, 52(4): 550-557. Accessed 24 May 2021.

Jahangir MA, P Bhisht, A Muheem, SS Imam (2017) Diabetes: pharmacological history and future management strategies. Pharm Bioprocess, 5(4): 054-065. Accessed 27 May 2021.

James J, RK pollom, I Hadjiyianni, G Buchholz, BL Reed (2017) Biosimilar insulins: what do you need to know? Inter Diabetes Nursing, 14: 33-35. doi: 10.1080/20573316.2017.1340246

Kasavadev J, B Saboo, MB Krishna, G Krisnan (2020) Evolution of insulin delivery de-vices: from syringes, pens, and pumps to DIY artificial pancreas. Diabetes Ther, 11: 1251-269. doi:

Kuhlmann M and A Schmidt (2014) Production and manufacturing of biosimilar insulin: implications for patients, physicians, and health care system. Biosimilars, 4: 45-58. doi:

Mane K, KC Chaluvaraju, MS Niranjan, Zaranappa, TR Manjuthej (2012) Review of insu-lin and its analogues in diabetesmellitus. J Clin Pharm, 003(002): 283-293. Accessed 31 May 2021.

Martin JH, A Russell, T O’Moore-Sullivan, JB Prins (2011) Insulin analogues: reviewing the pros and cons in managing diabetes mellitus. J Pharmacogenom Pharmacopro-teomics, 2(3):1-11. doi: 10.4172/2153-0645.1000106

Menengini L (2016) New insulin preparations: a primer for the clinician. Cleveland Clin J Med, 83(1): S27-S33. doi: 10.3949/ccjm.83.s1.05.

Owens DR (2011) Insulin preparations with prolonged effect. Diabetes Technol Ther, 13(1): S-5-S1-4. doi: 10.1089/dia.2011.0068

Pasquel FJ, MC lansang, K Dhatariya, GE Umpierrez (2021) Management of diabetes and hyperglycaemia in the hospital. Lancet Diabetes endocrinol, 9: 174-188. doi: S2213-8587(20)30381-8

Petznick A (2011) Insulin management of type 2 diabetes mellitus. Am Fam Phisician, 84(2):183-190. Ac-cessed 31 May 2021.

Poudel RS, S Shrestha, RM Piryani, B Basyal, K Kaucha, S Ahikari (2017) Assessment of insulin injection practice among diabetes patients in a tertiary healthcare centre in Nepal: a preliminary study. Hindawari J Diabetes Res, 1-6. doi:

Quianzon CC, I Cheikh (2012) History of insulin. J Community Hosp Intern Med Per-spectives, 2(18701): 1-3. doi:

Rachdaoui N (2020) Insulin: the friend and the foe in the development of type 2 diabetes mellitus. Int J Mol Sci, 21: 1-21. doi: 10.3390/ijms21051770

Riggs AD (2021) Making, cloning, and the expression of human insulin genes in bacteria: the path to humalin. Endocrine Rev, 42(3): 374-380.

Sandow J, W Landgraf, R Becker, G Seipke (2015) Equivalent recombinant human insu-lin preparations and their place in therapy. European Endocrinol, 11(1): 10-16. doi: 10.17925/EE.2015.11.01.10

Scholten BJ, FF Kreiner, SCL Gough, M Herrath (2021) Current and future therapies for type 1 diabetes. Diabetologia, 64: 1037-1048. doi:

Setty SG, Crasto W, Jarvis J, Khunti K, Davies MJ (2015) New insulin and newer insulin regimens: A review of their role in improving glycemic control in patients with diabe-tes. Postgraduate Med J, 92: 152-164. doi:10.1136/postgradmedj-2015-133716

Shen Y, W Prinyawiwatkul, Z Xu (2019) Insulin: a review of analytical methods. Royal Society Chem. doi:10.3949/ccjm.83.s1.05

Tibaldi JM (2014) Evolution of insulin: from human to analog. American J Med, 127(10A): S25-S38. doi: 10.1016/j.amjmed.2014.07.005

Vecchio I, C Tornali, NL Bragazzi, M Martini (2018) The discovery of insulin: an im-portant milestone in the history of medicine. Frontiers Endocrinol, 9(613): 1-8. doi: 10.3389/fendo.2018.00613

Ward CW, MC Lawrence (2011) Landmark in insulin research. Frontiers Endocrinol, 2(76): 1-11. doi: 10.3389/fendo.2011.00076

Zhang Y, J Yu, AR Kahkoska, J Wang, JB Buse, Zhen G (2019) Advances in transder-mal insulin delivery. Adv Drug Deliv Rev, 139:51-70. doi: 10.1016/j.addr.2018.12.006

Zijlstra E, L Heinemann, L Plum-Morschel (2014) Oral insulin reloaded: a structured ap-proach. J Diabetes Sci Technol, 8(3): 458-465. doi: 10.1177/1932296814529988

Most read articles by the same author(s)