Special 2021 Frontiers in Endocrinology Collection for the 100th Anniversary of Insulin Discovery

Currently, there are about 150–200 million diabetic patients treated with insulin globally. The year 2021 is special because the 100th anniversary of the insulin discovery is being celebrated. It is a good occasion to sum up the insulin pen technology invention and improvement which are nowadays the leading mode of an insulin delivery. Even though so many years have passed, insulin is still administered subcutaneously, that is why devices to deliver it are of great importance. Insulin pens have evolved only through the last decades (the reusable, durable pens, and the disposable, prefilled pens) and modern smart insulin pens have been developed in the last few years, and both types of the devices compared to traditional syringes and vials are more convenient, discrete in use, have better dosing accuracy, and improve adherence. In this review, we will focus on the history of insulin pens and their improvement over the previous decades.

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36 citations

The machines and methods for measuring skin were supplemented. A Samsung RS-80A ultrasonic diagnostic instrument and a L3-12AMHz linear array probe were applied for exploration. All subjects took the supine position, and the skin thickness was measured on the upper abdomen, lateral upper arm, and lateral thigh.

Original Research

29 April 2022

The Absorption of Needle-Free Insulin Aspart Through Jet Injector in Different Body Parts of Healthy Individuals

Qi Pan

, 5 more and

Lixin Guo

5,514 views

4 citations

(A) Landscape maturation: successive disulfide pairing enables a sequence of folding trajectories on ever-steeper funnel-shaped free-energy landscapes. (B) Ribbon model of insulin showing the three native disulfide bonds (yellow boxes). Coordinates were obtained from PDB entry 4INS (47). The A- and B chains are shown in light- and dark gray, respectively. (C) Stereo view of insulin with Cys substitutions highlighted in green (Table 1B). Side chains are shown as sticks; Cys-related sulfur atom and alpha-carbons of GlyA1 and GlyB8 represented as spheres (one-third Van der Waals radii).

Review

30 September 2021

Structural Lessons From the Mutant Proinsulin Syndrome

Balamurugan Dhayalan

, 2 more and

Michael A. Weiss

4,792 views

11 citations

PLA2G1B is released by pancreatic acinar cells into the pancreatic juice following a meal and then secreted into the intestinal lumen, where it eventually becomes activated. Phospholipid digestion by PLA2G1B results in elevated lysophosphatidylcholine (LPC), lysophosphatidic acid (LPA), and free fatty acids absorption in the portal blood, plasma, and liver, and increases hepatic very-low density lipoprotein (VLDL) production. Elevated enzymatic activity in the intestinal lumen can progress obesity, reduce glucose tolerance, and exacerbate insulin resistance – most notably due to elevated release/absorption of LPC and overarching dyslipidemia. PLA2G2E and PLA2G5 are expressed in WAT. 2 studies have contradicting results in PLA2G2Es metabolic role – 1 study discovered PLA2G2E increases ERK1/2 signaling and HSL phosphorylation to increase lipolysis, whereas Study 2 found PLA2G2E may promote obesity through hepatic lipogenesis and VLDL production. PLA2G5 preferentially hydrolyzes PC-rich phospholipids and promotes M2 macrophage polarization, which appears to have a beneficial impact on LDL lipid normalization and whole-body insulin sensitivity.

Mini Review

27 August 2021

Secretory Phospholipase A2s in Insulin Resistance and Metabolism

Michael S. Kuefner

5,352 views

18 citations

Glycerol-3-phosphate (Gro3P) is a central metabolite at the intersection of four important pathways in most cells: 1) glycolysis; 2) glycerolipid synthesis and the glycerolipid/free fatty acid (GL/FFA) cycle; 3) gluconeogenesis (liver and kidney) and 4) energy metabolism via electron transfer shuttle to mitochondria. Gro3P can be produced from glucose via glycolysis or from lipolysis-derived glycerol by glycerol kinase. The cellular levels and availability of Gro3P are regulated by Gro3P phosphatase (G3PP), which dephosphorylates Gro3P to form glycerol. Under conditions of excess glucose supply, a buildup of Gro3P in the cell may cause an overflow of glucose carbons into glycolysis, lipid synthesis and electron transfer, leading to accumulation of fat and also elevated production of reactive oxygen species (ROS) in mitochondria. G3PP may act as a detoxification enzyme to protect the cells from glucotoxicity, excess fat synthesis and storage and oxidative damage by hydrolyzing Gro3P to glycerol, a less harmful molecule, that exits the cell through aquaglyceroporins. α-KG, α-ketoglutarate; AQP, aquaglyceroporin; DHAP, dihydroxyacetone phosphate; ETC, electron transport chain; FFA, free fatty acid; G-6-P, glucose-6-phosphate; G3PP, glycerol-3-phosphate phosphatase; GA3P, glyceraldehyde-3-phosphate; GK, glycerol kinase; GL/FFA cycle, glycerolipid/free fatty acid cycle; Gro3P, glycerol-3-phosphate; OAA, oxaloacetate; ROS, reactive oxygen species; Succ-CoA, succinyl-CoA; TCA cycle, tricarboxylic acid cycle; TG, triglycerides.

Mini Review

13 July 2021

New Mammalian Glycerol-3-Phosphate Phosphatase: Role in β-Cell, Liver and Adipocyte Metabolism

Elite Possik

, 5 more and

Marc Prentki

17,655 views

25 citations

Review

04 June 2021

Insulin-Like Growth Factor Pathway and the Thyroid

Terry J. Smith

The insulin-like growth factor (IGF) pathway comprises two activating ligands (IGF-I and IGF-II), two cell-surface receptors (IGF-IR and IGF-IIR), six IGF binding proteins (IGFBP) and nine IGFBP related proteins. IGF-I and the IGF-IR share substantial structural and functional similarities to those of insulin and its receptor. IGF-I plays important regulatory roles in the development, growth, and function of many human tissues. Its pathway intersects with those mediating the actions of many cytokines, growth factors and hormones. Among these, IGFs impact the thyroid and the hormones that it generates. Further, thyroid hormones and thyrotropin (TSH) can influence the biological effects of growth hormone and IGF-I on target tissues. The consequences of this two-way interplay can be far-reaching on many metabolic and immunologic processes. Specifically, IGF-I supports normal function, volume and hormone synthesis of the thyroid gland. Some of these effects are mediated through enhancement of sensitivity to the actions of TSH while others may be independent of pituitary function. IGF-I also participates in pathological conditions of the thyroid, including benign enlargement and tumorigenesis, such as those occurring in acromegaly. With regard to Graves’ disease (GD) and the periocular process frequently associated with it, namely thyroid-associated ophthalmopathy (TAO), IGF-IR has been found overexpressed in orbital connective tissues, T and B cells in GD and TAO. Autoantibodies of the IgG class are generated in patients with GD that bind to IGF-IR and initiate the signaling from the TSHR/IGF-IR physical and functional protein complex. Further, inhibition of IGF-IR with monoclonal antibody inhibitors can attenuate signaling from either TSHR or IGF-IR. Based on those findings, the development of teprotumumab, a β-arrestin biased agonist as a therapeutic has resulted in the first medication approved by the US FDA for the treatment of TAO. Teprotumumab is now in wide clinical use in North America.

18,365 views

53 citations

Review

28 April 2021

The Interaction of Insulin and Pituitary Hormone Syndromes

Marie Helene Schernthaner-Reiter

, 2 more and

Anton Luger

Binding of glucose to the GLUT2 receptor increases oxidative metabolism and ATP synthesis, thereby leading to the closure of the KATP channels, which in turn stimulates membrane depolarization and insulin secretion. Cortisol binds to and activates the glucocorticoid receptor, which translocates to the nucleus and initiates several cascades culminating in repression of insulin transcription and inhibition of insulin release. In addition, cortisol further deteriorates beta-cell function by reducing GLP-1 production and its positive effects on insulin secretion, and by increasing the secretion of somatostatin, which in turn negatively impacts insulin gene transcription and insulin secretion. Dashed lines represent indirect effects. ATP, adenosine triphosphate; Ca, Calcium; GLP-1, glucagon-like peptide 1; GLP-1R, glucagon-like peptide 1 receptor; GLUT2, glucose transporter 2; GR, glucocorticoid receptor; GRE, glucocorticoid response element.

Pituitary hormone axes modulate glucose metabolism and exert direct or indirect effects on insulin secretion and function. Cortisol and growth hormone are potent insulin-antagonistic hormones. Therefore impaired glucose tolerance, elevated fasting glucose concentrations and diabetes mellitus are frequent in Cushing’s disease and acromegaly. Also prolactinomas, growth hormone (GH) deficiency, hypogonadism and hypothyroidism might be associated with impaired glucose homeostasis but usually to a lesser extent. Therefore glucose metabolism needs to be closely monitored and treated in patients with pituitary adenomas. Correction of the pituitary dysfunction is frequently followed by improvement of glucose homeostasis.

27,788 views

20 citations