New Advances in Insulin—100 Years since Its Discovery

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 6846

Special Issue Editor


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Guest Editor
1. Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia
2. School of Medicine, University of Zagreb, Zagreb, Croatia
Interests: diabetes type 1; diabetes type 2; metabolic syndrome; diabetic nephropathy; diabetic retinopathy
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Special Issue Information

Dear Colleagues,

The discovery of insulin in 1921 represented a milestone in the treatment of diabetes. In 1923, the Nobel Prize for Medicine was awarded for its discovery, and it was one of the most important discoveries in the history of medical science because it affected hundreds of millions of people worldwide. Thousands of lives have been saved and the life expectancy of people with diabetes has been significantly extended. Since its discovery, insulin has been continuously improved through pharmacological development and optimized for therapeutic purposes, including the development of intermediate- and long-acting insulins, the ability to produce human insulin, and finally, the development of insulin analogs with improved properties using recombinant DNA technology.

Despite increasing awareness, diabetes is still one of the most challenging health problems in the 21st century. In the last 15 years, the number of people diagnosed with type 1 diabetes increased by 45%, and those diagnosed with type 2 diabetes increased by 95%. Although, recently, the focus in the treatment of diabetes has been directed to new therapeutic options, insulin is still one of the most potent therapeutic options for patients with type 2 diabetes, and the only one for patients with type 1 diabetes.

Considering this context, this Special Issue will focus on the roles of insulin and insulin action in a broad sense. We welcome submissions related to the new knowledge about insulin secretion and action, the development and action of insulin analogs, and their effects on glycemic control and chronic complications of diabetes.

Dr. Tomislav Bulum
Guest Editor

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Keywords

  • insulin action
  • insulin analogs
  • type 1 diabetes
  • type 2 diabetes
  • complications
  • glucose homeostasis

Published Papers (6 papers)

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Research

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18 pages, 15636 KiB  
Article
A Pilot Study on the Proteomics Profile of Serum Exosome-Enriched Extracellular Vesicles from Normal versus Individuals with Obesity-Related Insulin Resistance
by Viswanathan Saraswathi, Weilun Ai, Vikas Kumar, Kanika Sharma, Thiyagarajan Gopal, Narendra Kumar, Harmeet Malhi, Tejasav Sehrawat and Cyrus V. Desouza
Biomedicines 2024, 12(4), 799; https://doi.org/10.3390/biomedicines12040799 - 3 Apr 2024
Viewed by 978
Abstract
Objective: Circulating exosome-enriched extracellular vesicles (EVs) have drawn considerable importance in obesity-related insulin-resistance (IR). We sought to compare the proteomics profile of serum exosomes from normal individuals and those with obesity and IR. Methods: We isolated serum exosomes from male subjects with obesity [...] Read more.
Objective: Circulating exosome-enriched extracellular vesicles (EVs) have drawn considerable importance in obesity-related insulin-resistance (IR). We sought to compare the proteomics profile of serum exosomes from normal individuals and those with obesity and IR. Methods: We isolated serum exosomes from male subjects with obesity and insulin resistance (Ob-IR, HOMA-IR > 2.0) and lean/overweight insulin-sensitive (Normal (N), HOMA-IR < 2.0) individuals. The differential protein expression between the two groups was detected by a label-free quantitative mass spectrometry analysis followed by GO annotation and ingenuity pathway analysis (IPA). Results: We identified 23 upregulated and 46 downregulated proteins between Ob-IR and N groups. Some of these proteins are involved in altering insulin signaling (VPS13C, TBC1D32, TTR, and ADIPOQ), inflammation (NFκB and CRP), and B-cell proliferation/activation (IGLV4-69, IGKV1D-13, and IGHV4-28). GO analysis revealed that the differentially expressed proteins (DEPs) are mainly involved in regulating immune cell activation and are located in extracellular space. IPA analysis showed that top molecules mediating IR, inflammation and B-cell activation were upregulated in Ob-IR subjects compared to N subjects. Conclusions: Serum exosomal proteins can be used as biomarkers to identify the future risk of diabetes and a therapeutic target to prevent or slow down the progression of diabetes in high-risk individuals. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years since Its Discovery)
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28 pages, 2666 KiB  
Article
Insulin and Metformin Administration: Unravelling the Multifaceted Association with Mortality across Various Clinical Settings Considering Type 2 Diabetes Mellitus and COVID-19
by Łukasz Lewandowski, Agnieszka Bronowicka-Szydełko, Maciej Rabczyński, Dorota Bednarska-Chabowska, Joanna Adamiec-Mroczek, Adrian Doroszko, Małgorzata Trocha, Krzysztof Kujawa, Agnieszka Matera-Witkiewicz, Edwin Kuźnik, Paweł Lubieniecki, Marcin Madziarski, Janusz Sokołowski, Ewa A. Jankowska and Katarzyna Madziarska
Biomedicines 2024, 12(3), 605; https://doi.org/10.3390/biomedicines12030605 - 7 Mar 2024
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Abstract
Due to the molecular mechanisms of action of antidiabetic drugs, they are considered to be effective in the treatment of both COVID-19 and the post-COVID-19 syndromes. The aim of this study was to determine the effect of administering insulin and metformin on the [...] Read more.
Due to the molecular mechanisms of action of antidiabetic drugs, they are considered to be effective in the treatment of both COVID-19 and the post-COVID-19 syndromes. The aim of this study was to determine the effect of administering insulin and metformin on the mortality of patients with type 2 diabetes (T2DM) with symptomatic COVID-19 with the use of logistic regression models. The association between death and insulin and metformin was weak and could not be included in the multivariate model. However, the interaction of both drugs with other factors, including remdesivir and low-molecular-weight heparin (metformin), age and hsCRP (insulin), modulated the odds of death. These interactions hint at multifaceted (anti-/pro-) associations of both insulin and metformin with the odds of death, depending on the patient’s characteristics. In the multivariate model, RDW-SD, adjusted with low-molecular-weight heparin treatment, age, sex and K+, was associated with mortality among patients with COVID-19 and T2DM. With a 15% increase in RDW-SD, the risk of death increased by 87.7%. This preliminary study provides the foundations for developing further, more personalized models to assess the risk of death in T2DM patients, as well as for identifying patients at an increased risk of death due to COVID-19. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years since Its Discovery)
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12 pages, 2865 KiB  
Article
In Association with Other Risk Factors, Smoking Is the Main Predictor for Lower Transcutaneous Oxygen Pressure in Type 2 Diabetes
by Tomislav Bulum, Neva Brkljačić, Angelika Tičinović Ivančić, Maja Čavlović, Ingrid Prkačin and Martina Tomić
Biomedicines 2024, 12(2), 381; https://doi.org/10.3390/biomedicines12020381 - 7 Feb 2024
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Abstract
Type 2 diabetes mellitus (T2DM) significantly increases the risk of peripheral artery disease (PAD), and diabetes is the leading cause of nontraumatic amputations. This study investigated the risk factors for transcutaneous oxygen pressure (TcPO2) in T2DM, a noninvasive method to quantify skin oxygenation [...] Read more.
Type 2 diabetes mellitus (T2DM) significantly increases the risk of peripheral artery disease (PAD), and diabetes is the leading cause of nontraumatic amputations. This study investigated the risk factors for transcutaneous oxygen pressure (TcPO2) in T2DM, a noninvasive method to quantify skin oxygenation and the underlying microvascular circulation. The study included 119 T2DM patients (91 male/28 female). TcPO2 measurements were conducted with the Tina TCM4 Series transcutaneous monitor (Radiometer, Copenhagen, Sweden) and skin electrodes. Patients with TcPO2 < 40 mmHg were younger (p = 0.001), had significantly higher systolic blood pressure (SBP) (p = 0.023), glycated hemoglobin (HbA1c) (p = 0.013), fasting plasma glucose (fPG) (p = 0.038), total cholesterol (p = 0.006), LDL cholesterol (p = 0.004), and had more frequent smoking habits (p = 0.001) than those with TcPO2 ≥ 40 mmHg. The main predictors for the TcPO2 value (R2 = 0.211) obtained via stepwise regression analysis were age, smoking, SBP, HbA1c, fPG, and total and LDL cholesterol. Among all the listed predictors, smoking, HbA1c, and LDL cholesterol were found to be the most significant, with negative parameter estimates of −3.051310 (p = 0.0007), −2.032018 (p = 0.0003), and −2.560353 (p = 0.0046). The results of our study suggest that in association with other risk factors, smoking is the main predictor for lower TcPO2 in T2DM. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years since Its Discovery)
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13 pages, 674 KiB  
Article
Hyperglycaemia and Its Prognostic Value in Patients with COVID-19 Admitted to the Hospital in Lithuania
by Lina Zabuliene, Ieva Kubiliute, Mykolas Urbonas, Ligita Jancoriene, Jurgita Urboniene and Ioannis Ilias
Biomedicines 2024, 12(1), 55; https://doi.org/10.3390/biomedicines12010055 - 25 Dec 2023
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Abstract
Background and objectives: Increased blood glucose levels atadmission are frequently observed in COVID-19 patients, even in those without pre-existing diabetes. Hyperglycaemia is associated with an increased incidence of severe COVID-19 infection. The aim of this study was to evaluate the association between hyperglycaemia [...] Read more.
Background and objectives: Increased blood glucose levels atadmission are frequently observed in COVID-19 patients, even in those without pre-existing diabetes. Hyperglycaemia is associated with an increased incidence of severe COVID-19 infection. The aim of this study was to evaluate the association between hyperglycaemia at admission with the need for invasive mechanical ventilation (IMV) and in-hospital mortality in patients without diabetes who were hospitalized for COVID-19 infection. Materials and methods: This retrospective observational study was conducted at Vilnius University Hospital Santaros Clinics, Lithuania with adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 and were hospitalized between March 2020 and May 2021. Depersonalized data were retrieved from electronic medical records. Based on blood glucose levels on the day of admission, patients without diabetes were divided into 4 groups: patients with hypoglycaemia (blood glucose below 4.0 mmol/L), patients with normoglycaemia (blood glucose between ≥4.0 mmol/L and <6.1 mmol/L), patients with mild hyperglycaemia (blood glucose between ≥6.1 mmol/L and <7.8 mmol/L), and patients with intermittent hyperglycaemia (blood glucose levels ≥7.8 mmol/L and <11.1 mmol/L). A multivariable binary logistic regression model was created to determine the association between hyperglycaemia and the need for IMV. Survival analysis was performed to assess the effect of hyperglycaemia on outcome within 30 days of hospitalization. Results: Among 1945 patients without diabetes at admission, 1078 (55.4%) had normal glucose levels, 651 (33.5%) had mild hyperglycaemia, 196 (10.1%) had intermittent hyperglycaemia, and 20 (1.0%) had hypoglycaemia. The oddsratio (OR) for IMV in patients with intermittent hyperglycaemia was 4.82 (95% CI 2.70–8.61, p < 0.001), and the OR was 2.00 (95% CI 1.21–3.31, p = 0.007) in those with mild hyperglycaemia compared to patients presenting normal glucose levels. The hazardratio (HR) for 30-day in-hospital mortality in patients with mild hyperglycaemia was 1.62 (95% CI 1.10–2.39, p = 0.015), while the HR was 3.04 (95% CI 2.01–4.60, p < 0.001) in patients with intermittent hyperglycaemia compared to those with normoglycaemia at admission. Conclusions: In COVID-19 patients without pre-existing diabetes, the presence of hyperglycaemia at admission is indicative of COVID-19-induced alterations in glucose metabolism and stress hyperglycaemia. Hyperglycaemia at admission in COVID-19 patients without diabetes is associated with an increased risk of invasive mechanical ventilation and in-hospital mortality. This finding highlights the importance for clinicians to carefully consider and select optimal support and treatment strategies for these patients. Further studies on the long-term consequences of hyperglycaemia in this specific population are warranted. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years since Its Discovery)
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Review

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16 pages, 1380 KiB  
Review
What Is the Role of Basal Weekly Insulin in Clinical Practice? The State of the Art
by Christiano Argano, Laura Priola, Francesco Manno and Salvatore Corrao
Biomedicines 2024, 12(4), 900; https://doi.org/10.3390/biomedicines12040900 - 18 Apr 2024
Viewed by 746
Abstract
Despite the advent of innovative therapies in the treatment of diabetes, ever-increasing awareness is still directed to the role of insulin since it has continued to be at the centre of diabetes therapy for decades, as a therapeutic integration of innovative agents in [...] Read more.
Despite the advent of innovative therapies in the treatment of diabetes, ever-increasing awareness is still directed to the role of insulin since it has continued to be at the centre of diabetes therapy for decades, as a therapeutic integration of innovative agents in type 2 diabetes mellitus (T2DM), as the only replacement therapy in type 1 diabetes mellitus (T1DM) and also in gestational diabetes. In this context, the study of molecules such as weekly basal insulins, both for their technological and pharmacodynamic innovation and their manageability and undoubted benefits in compliance with drug therapy, can only be a turning point in diabetes and for all its phenotypes. This review aims to provide insight into the knowledge of basal weekly insulins and their use in type 1 and 2 diabetes mellitus by examining their safety, efficacy, manageability and increased therapeutic compliance. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years since Its Discovery)
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13 pages, 26225 KiB  
Review
100 Years since the Discovery of Insulin, from Its Discovery to the Insulins of the Future
by Carmen Lambert and Elias Delgado
Biomedicines 2024, 12(3), 533; https://doi.org/10.3390/biomedicines12030533 - 27 Feb 2024
Viewed by 1350
Abstract
The term diabetes first emerged in the 3rd century BC, in a reference by Demetrius of Apamea, who described the disease as a dropsy in which any liquid ingested is eliminated in the form of urine. However, the great discovery that revolutionized this [...] Read more.
The term diabetes first emerged in the 3rd century BC, in a reference by Demetrius of Apamea, who described the disease as a dropsy in which any liquid ingested is eliminated in the form of urine. However, the great discovery that revolutionized this field came from the Canadian doctor Frederick Banting, who together with his student and assistant Charles Best, managed to isolate insulin and treat a patient with diabetes on 23 January 1922. This patient was Leonard Thompson, and the results obtained from him were surprising. His glycosuria and ketonuria disappeared and his blood glucose returned to normal. He received daily injections and lived 13 more years. Advances in the treatment of diabetes have been numerous in the 100 years since its discovery. In this review, we recapitulate the most important events that have occurred, and where research is progressing today. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years since Its Discovery)
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