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Diabetes mellitus Type 2 (DM2T) is a rapidly expanding metabolic endocrine disorder worldwide. It is caused due to inadequate insulin secretion by pancreatic beta cells as well as development of insulin resistance. This study aimed to investigate the anti-α-glucosidase, insulin stabilization effect, and non-cytotoxic nature of Gymnema latifolium leaf aqueous extract (GLAE). FTIR analysis revealed the functional groups of compounds present in GLAE. Through LC/ESI-MS/MS analysis, about 12 compounds which belongs to different classes, triterpene glycosides, flavonoids, phenolics, stilbene glycosides and chlorophenolic glycosides were identified. GLAE showed in vitro antioxidant activity. GLAE stabilized insulin by increasing its α-helical content. GLAE inhibited the mammalian α-glucosidase (IC 50 = 144 μg/mL) activity through competitive mode (Ki = 61.30 µg/mL). GLAE did not affect the viability of normal cell line (Vero cell line) which shows its non-toxic nature. Molecular docking of phytocompounds identified in GLAE was done with human α-glucosidase and insulin. The top 2 compounds [Gymnema saponin V (GSV) and quercetin 3-(2-galloylglucoside) (QGG) with α-glucosidase; GSV and Z)-resveratrol 3,4'-diglucoside (RDG) with human insulin] with low binding free energy were subjected to 100 ns molecular dynamics simulation to ascertain the stable binding of ligand with protein. The MM/GBSA analysis revealed binding free energy of GSV/α-glucosidase and QGG /α-glucosidase to be - 20.9935 and, - 30.9461 kcal/mol, respectively. Altogether GLAE is valuable source of anti-α-glucosidase inhibitors and insulin stabilizing compounds, suggesting potential lead for further exploration as complementary medicine against DM2T., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.Natarajan reports equipment, drugs, or supplies was provided by Periyar University. Shahanaj Ismail reports a relationship with Periyar University that includes: non-financial support. The authors declare that no conflict of interests to publish an article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To evaluate and compare the antidiabetic and antioxidant activities of fruit pulp extracts from Cucurbita moschata (PCMOS) and Cucurbita maxima (PCMAX)., Methods: The antidiabetic activity was carried out in vivo by orally and daily giving the extracts at a dose of 500 mg/kg·b.w. to the streptozotocin-induced diabetic male albino Wistar rats for six weeks. After the period of administration, blood glucose levels, body weight, serum insulin, morphology of islets of Langerhans, biochemical parameters, and haematological values of the rats were determined. Meanwhile, the antioxidant activity was carried out in vitro by determination of total phenolic and flavonoid contents, DPPH radical scavenging activity, and ferric reducing antioxidant power., Results: PCMAX significantly ( p < 0.05) reduced blood glucose levels but increased the body weight, serum insulin levels, size and number of islets of Langerhans, and β -cell number of the treated diabetic rats more than PCMOS did. However, they did not alter biochemical parameters and haematological values of the treated diabetic rats. PCMAX possessed total phenolic and flavonoid contents and showed DPPH scavenging and FRAP reducing antioxidant power more significantly ( p < 0.05) than PCMOS., Conclusions: According to the obtained results, it is indicated that PCMOS and PCMAX possess antidiabetic and antioxidant activities. PCMAX possesses more potent antidiabetic and antioxidant activities than PCMOS. These are probably due to PCMAX providing polysaccharide and total phenolic and flavonoid contents more than PCMOS., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Apinya Suwannapong et al.)

The endocrine system influences all tissues and cells in the human body. The ocular surface is constantly exposed to circulating hormones and expresses their specific receptors. Dry eye disease (DED) is a disorder with multifactorial etiology, and endocrine anomalies are one of the inciting factors. The endocrine anomalies that cause DED include physiological conditions such as menopause, menstrual cycle variations, pathologies such as polycystic ovarian syndrome, androgen resistance, iatrogenic conditions such as contraceptive use, and antiandrogen treatment. This review highlights the status of these hormones in DED along with the mechanism of action of different hormones on the ocular surface structures and the clinical implications of these effects. The influence of androgens, estrogens, and progesterone on the ocular surface tissues, and the implications of androgen-deficient states in DED are also discussed. The physiological and pathological effects of menopause and sex hormone replacement therapy are discussed. The effects of insulin and insulin resistance on the ocular surface and DED, and the growing potential of topical insulin therapeutics for DED are mentioned. Thyroid-associated ophthalmopathy, its impact on the ocular surface, and the tissue effects of thyroid hormone in the context of DED are reviewed. Finally, the potential role of hormonal therapeutics in the management of DED has also been discussed. The compelling evidence suggests that it would be clinically beneficial to consider the possibility of hormonal imbalances and their impact while treating patients with DED., Competing Interests: None

The skin of amphibians is a tissue with biological functions, such as defense, respiration, and excretion. In recent years, researchers have discovered a large number of peptides in the skin secretions of amphibians, including antimicrobial peptides, antioxidant peptides, bradykinins, insulin-releasing peptides, and other peptides. This review focuses on the origin, primary structure, secondary structure, length, and functions of peptides secreted from amphibians' skin. We hope that this review will provide further information and promote the further study of amphibian skin secretions, in order to provide reference for expanding the research and application of amphibian bioactive peptides.

In this study, the caprine pancreas has been presented as an alternative to the porcine organ for pancreatic xenotransplantation with lesser risk factors. The obtained caprine pancreas underwent a systematic cycle of detergent perfusion for decellularization. It was perfused using anionic (0.5% w/v sodium dodecyl sulfate) as well as non-ionic (0.1% v/v triton X-100, t-octyl phenoxy polyethoxy ethanol) detergents and washed intermittently with 1XPBS supplemented with 0.1% v/v antibiotic and nucleases in a gravitation-driven set-up. After 48 h, a white decellularized pancreas was obtained, and its extracellular matrix (ECM) content was examined for scaffold-like properties. The ECM content was assessed for removal of cellular content, and nuclear material was evaluated with temporal H&E staining. Quantified DNA was found to be present in a negligible amount in the resultant decellularized pancreas tissue (DPT), thus prohibiting it from triggering any immunogenicity. Collagen and fibronectin were confirmed to be preserved upon trichrome and immunohistochemical staining, respectively. SEM and AFM images reveal interconnected collagen fibril networks in the DPT, confirming that collagen was unaffected. sGAG was visualized using Prussian blue staining and quantified with DMMB assay, where DPT has effectively retained this ECM component. Uniaxial tensile analysis revealed that DPT possesses better elasticity than NPT (native pancreatic tissue). Physical parameters like tensile strength, stiffness, biodegradation, and swelling index were retained in the DPT with negligible loss. The cytocompatibility analysis of DPT has shown no cytotoxic effect for up to 72 h on normal insulin-producing cells (MIN-6) and cancerous glioblastoma (LN229) cells in vitro. The scaffold was recellularized using isolated mouse islets, which have established in vitro cell proliferation for up to 9 days. The scaffold received at the end of the decellularization cycle was found to be non-toxic to the cells, retained biological and physical properties of the native ECM, suitable for recellularization, and can be used as a safer and better alternative as a transplantable organ from a xenogeneic source., (© 2022 Federation of American Societies for Experimental Biology.)

Men with diabetes have negative effects on reproduction that causes sexual dysfunction. Medicinal plants are non-toxic and much safer than synthetic drugs because regular use of synthetic drugs shows long-term side effects. Curcuma amada (Roxb) is a medicinal plant used in Ayurveda and Unani medicinal systems in India. The goal of this study is to rummage the potential efficiency of the most potent solvent fraction of effective extract of hydro-methanol 60:40 of C. amada rhizome on male gonadal hypofunction in streptozotocin-induced diabetic rat. Diabetes-induced testicular hypofunction was evaluated by glycemic, spermiological, biochemical, genomic, flow cytometric, and histology of testicular tissue. The n-hexane, chloroform, ethyl-acetate, and n-butanol solvent fractions of the said extract were administrated for 4 weeks at 10 mg dose/100 g body weight/day. Among all the used fractions, the ethyl-acetate solvent fraction-treated group showed maximum recovery in serum insulin (177.42%), sperm count (92.84%), sperm motility (97.15%), and serum testosterone (164.33%). The diabetic rats treated with ethyl-acetate solvent fraction also exhibited the maximum resettlement in flow cytometric analysis of sperm viability (55.84%) and sperm mitochondrial integrity (149.79%), gene expression patterns of key markers for androgenesis (Δ5, 3β-HSD 87.50%, and 17β-HSD 74.66%) and apoptosis (Bax 44.63%, Bcl-2 54.03%, and Caspase-3 35.77%) along with testicular histology. The ethyl-acetate fraction contains alkaloids, flavonoids, and polyphenols where all of these components are not present in other fractions, may be the most effective cause for the recovery of diabetes-linked oxidative stress-mediated testicular hypofunctions. PRACTICAL APPLICATIONS: Nowadays worldwide, the use of synthetic drugs are reduced due to their toxic effect. At present, synthetic drugs are replaced by several herbal drugs, the natural source of medicine which has many therapeutic values. C. amada has strong antioxidant activity due to the presence of bio-active compound(s) that can able to manage streptozotocin-induced diabetes linked to oxidative damage of male gonadal organs. Therefore, these bio-active compound(s)-containing said medicinal plant may use as a good source of antioxidative food in the food industry as nutraceuticals and in pharmaceutical industries for the development of the herbal drug to manage diabetes-linked male gonadal hypofunctions. At present, WHO also gives emphasis for developing one drug-multi-disease therapy. From such a viewpoint, this active fraction-containing phytomolecules may have corrective efficacy against diabetes as well as oxidative stress-linked testicular complications., (© 2022 Wiley Periodicals LLC.)

Four previously undescribed iridoid glycosides neocornuside A-D ( 1-4 ), along with six known ones ( 5-10 ), were isolated from Cornus officinalis fruit. Their structures were elucidated by extensive spectroscopic (NMR, UV, IR, and MS) analysis and comparison with data reported in the literature. All isolates were assessed for their antidiabetic activity on the relative glucose consumption in insulin-induced insulin-resistant HepG2 cells. The results showed that compounds 1 , 3 , and 7 exhibited significant antidiabetic activities with EC 50 values of 0.582, 1.275, and 0.742 μM, respectively. Moreover, compounds 1 , 3 , and 7 could improve the ability of 2-NBDG uptake of insulin-induced HepG2 cells.

Objectives: To assess the ameliorative activity of polyphenolic-rich extracts of Basella rubra leaves on β-cell dysfunction in type-II diabetes (T2DM)., Methods: Total phenolic and flavonoid contents; α-amylase and α-glucosidase inhibitory actions and qualitative analysis of the bioactive compounds of the polyphenolic-rich extract of B. rubra leaves were investigated using gas chromatography-mass spectroscopy (GC-MS). Diabetes mellitus (DM) was induced by single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and the rats were orally given bound phenolic (BPE) and free phenolic extracts (FPE) of B. rubra (B.R) leaves at 200 and 400 mg/kg b.w once daily for 14 days. Biochemical analyses were executed for evaluation of serum insulin, serum lipid profile concentrations, liver enzymes activities., Results: The extracts demonstrated antioxidant potentials and enzymes inhibitory activities in dose dependent manner; and several bioactive compounds as revealed by GC-MS. BPE and FPE considerably (p<0.05) reduced hyperglycemia, improved serum insulin levels, ameliorated the concentration of serum lipid profiles and improved liver antioxidant activities. Additionally, BPE and FPE expressively decreased alanine aminotransferases (ALT), aspartate aminotransferases (AST), gamma-glutamyl transferase (GGT) activities along with levels of bilirubin and urea when compare to diabetic control rats., Conclusions: Data acquired exhibited the ability of BPE and FPE to improve pancreatic beta-cell in streptozotocin-induced rats., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Insulin has been available for the treatment of diabetes for almost a century, and the variety of insulin choices today represents many years of discovery and innovation. Insulin has gone from poorly defined extracts of animal pancreata to pure and precisely controlled formulations that can be prescribed and administered with high accuracy and predictability of action. Modifications of the insulin formulation and of the insulin molecule itself have made it possible to approximate the natural endogenous insulin response. Insulin and insulin formulations had to be designed to produce either a constant low basal level of insulin or the spikes of insulin released in response to meals. We discuss how the biochemical properties of endogenous insulin were exploited to either shorten or extend the time-action profiles of injectable insulins by varying the pharmacokinetics (time for appearance of insulin in the blood after injection) and pharmacodynamics (time-dependent changes in blood sugar after injection). This has resulted in rapid-acting, short-acting, intermediate-acting, and long-acting insulins, as well as mixtures and concentrated formulations. An understanding of how various insulins and formulations were designed to solve the challenges of insulin replacement will assist clinicians in meeting the needs of their individual patients., (© Endocrine Society 2020.)

The applicability of capillary zone electrophoresis (CZE) for the separation of the deamidated forms of insulin has been studied. 50 mM NH 4 Ac (pH=9) with 20 % v/v isopropylalcohol was found optimal for efficient separation of insulin from its even 10 deamidated forms. The developed method was efficiently applied for monitoring the degradation rate of insulin and the formation of different deamidation isoforms. Two months after the acidification more than thirty peaks can be observed in the electropherogram, because degradation products other than deamidated components were formed as well. The recorded mass spectra enabled us to assign the exact mass of the components, and thus the identification of insulin isoforms could be accomplished. We think that this study provides useful information on how the determination of several deamidation forms can be carried out with CE-MS, but the identification of the exact position of deamidation sites in the insulin molecule remains a challenge., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Commercially available silica-based monolithic columns Chromolith RP-8e, Chromolith RP-18, and Chromolith HR RP-18, and polymer-based monolithic columns ProSwift RP-1S, ProSwift RP-2H, and ProSwift RP-3U varying in pore size and bonded phase have been tested for the fast separation of selected sets of analytes. These mixtures of analytes included small molecules (uracil, caffeine, 1-phenylethanol, butyl paraben, and anthracene), acylated insulins, and intact proteins (ribonuclease A, cytochrome C, transferrin, apomyoglobin, and thyroglobulin), and covered wide range of chemistries and sizes. Small molecules were well separated with a height equivalent to theoretical plate of 11-26 μm using silica-based monolithic columns, while organic polymer-based monoliths excelled in the fast sub 1 min baseline separations of large molecules. A peak capacity of 37 was found for separation of acylated insulins on Chromolith columns using a 3 min gradient at a flow rate of 3 ml/min. Poor recovery of proteins from Chromolith columns and significant peak tailing of small molecules using ProSwift columns were the major obstacles in using monolithic columns in those applications., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Label-free optical detection of insulin would allow in vitro assessment of pancreatic cell functions in their natural state and expedite diabetes-related clinical research and treatment; however, no existing method has met these criteria at physiological concentrations. Using spatially uniform 3D gold-nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of insulin in the secretions from human pancreatic islets under low and high glucose environments without the use of labels such as antibodies or aptamers. Label-free measurements of the islet secretions showed excellent correlation among the ambient glucose levels, secreted insulin concentrations, and measured Raman-emission intensities. When excited at 785 nm, plasmonic hotspots of the densely arranged 3D gold-nanoparticle pillars as well as strong interaction between sulfide linkages of the insulin molecules and the gold nanoparticles produced highly sensitive and reliable insulin measurements down to 100 pM. The sensors exhibited a dynamic range of 100 pM to 50 nM with an estimated detection limit of 35 pM, which covers the reported concentration range of insulin observed in pancreatic cell secretions. The sensitivity of this approach is approximately 4 orders of magnitude greater than previously reported results using label-free optical approaches, and it is much more cost-effective than immunoassay-based insulin detection widely used in clinics and laboratories. These promising results may open up new opportunities for insulin sensing in research and clinical applications.

Background: Feed intake affects the GH-IGF system and may be a key factor in determining the ovarian follicular growth rate. In fat mares, the plasma IGF-1 concentration is high with low GH and a quick follicular growth rate, in contrast to values observed in thin mares. Nothing is known regarding the long-term effects of differential feed intake on the IGF system. The objective of this experiment was to quantify IGFs, IGFBPs, GH, glucose, insulin, gonadotropin and progesterone (P4) in blood and in preovulatory follicular fluid (FF) in relation to feeding levels in mares., Methods: Three years prior to the experiment, Welsh Pony mares were assigned to a restricted diet group (R, n = 10) or a well-fed group (WF, n = 9). All mares were in good health and exhibited differences in body weight and subcutaneous fat thickness. Follicular development was scanned daily and plasma was also collected daily. Preovulatory FF was collected by ultrasound-guided follicular aspiration. Hormone levels were assayed in FF and plasma with a validated RIA., Results: According to scans, the total number of follicles in group R was 53% lower than group WF. Insulin and IGF-1 concentrations were higher in WF than in R mares. GH and IGF-2 concentrations were lower in plasma from WF mares than from R mares, but the difference was not significant in FF. The IGFBP-2/IGFBP-3 ratio in FF was not affected by feeding but was dramatically increased in R mare plasma. No difference in gonadotropin concentration was found with the exception of FSH, which was higher in the plasma of R mares. On the day of puncture, P4 concentrations were not affected by feeding but were higher in preovulatory FF than in plasma., Conclusions: The bioavailability of IGF-1 or IGF-2, represented by the IGFBP2/IGFBP3 ratio, is modified by feed intake in plasma but not in FF. These differences partially explain the variability in follicular growth observed between well-fed mares and mares on restricted diets.

Differentiation of insulin analogues is required in forensic and clinical toxicology as well as in sports doping control. Immunoassay results provide only weak evidence for exogenous administration of insulin, as concentrations cannot be reliably interpreted and specific information on the insulin species remains unknown. In post-mortem blood, insulin degrades rapidly. In this study, improved methodology consisting of precipitation of proteins, immunoaffinity purification and liquid chromatography coupled to high resolution/high accuracy mass spectrometry were applied to post-mortem vitreous humour. Ten successive cases with a post-mortem interval from four to ten days were investigated for insulin analogues. The cause of death in these cases was connected with diabetes and its complications, as well as with chronic cardiovascular disease, alcoholism and cancer. In all cases, the manner of death was natural (disease). Insulin was positively detected in post-mortem vitreous humour in three cases out of ten by mass spectrometry. In two cases, the method revealed the long-acting insulin glargine (Lantus) metabolite M2 (DesB31-32 Lantus), and human insulin was detected in one case. The findings were in agreement with the documented history of insulin medication. No other obvious reason could be found for the failure of detecting insulins in the other cases than insulin degradation during the lengthy post-mortem interval. Vitreous humour is still a most prospective specimen for detection of insulin analogues post-mortem., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

High-level production of heterologous proteins is likely to impose a metabolic burden on the host cell and can thus affect various aspects of cellular physiology. A data-driven approach was applied to study the secretory production of a human insulin analog precursor (IAP) in Saccharomyces cerevisiae during prolonged cultivation (80 generations) in glucose-limited aerobic chemostat cultures. Physiological characterization of the recombinant cells involved a comparison with cultures of a congenic reference strain that did not produce IAP, and time-course analysis of both strains aimed at identifying the metabolic adaptation of the cells towards the burden of IAP production. All cultures were examined at high cell density conditions (30 g/L dry weight) to increase the industrial relevance of the results. The burden of heterologous protein production in the recombinant strain was explored by global transcriptome analysis and targeted metabolome analysis, including the analysis of intracellular amino acid pools, glycolytic metabolites, and TCA intermediates. The cellular re-arrangements towards IAP production were categorized in direct responses, for example, enhanced metabolism of amino acids as precursors for the formation of IAP, as well as indirect responses, for example, changes in the central carbon metabolism. As part of the long-term adaptation, a metabolic re-modeling of the IAP-expressing strain was observed, indicating an augmented negative selection pressure on glycolytic overcapacity, and the emergence of mitochondrial dysfunction. The evoked metabolic re-modeling of the cells led to less optimal conditions with respect to the expression and processing of the target protein and thus decreased the cellular expression capacity for the secretory production of IAP during prolonged cultivation., (Copyright © 2013 Wiley Periodicals, Inc.)