Search Results (23)

Background/Objectives: Inflammatory bowel disease (IBD) represents a growing therapeutic challenge, and the identification of novel treatment strategies remains an unmet clinical need. Drug repurposing offers a pragmatic and cost-effective alternative to de novo drug development. This study aimed to identify candidate drugs for repurposing in IBD through inverse signal detection within a large spontaneous pharmacovigilance database. Methods: In this observational, retrospective pharmacovigilance study, data from the FDA Adverse Event Reporting System (FAERS) were analyzed using OpenVigil 2.1. Drugs inversely associated with IBD were identified based on a ROR < 1 and an adjusted p-value < 0.05. Candidates were subsequently filtered to exclude agents with implausible indications, unfavorable pharmacokinetic profiles, or recognized contraindications to use in IBD. Although this screening process yielded a broader set of repurposing candidates across multiple drug classes, the present study focused specifically on antidiabetic medications, which were subjected to a targeted literature review evaluating their immunomodulatory properties, anti-inflammatory mechanisms, and existing preclinical and clinical evidence in the context of IBD. Results: Of 3585 initial drug–event combinations evaluated, 73 candidates met predefined criteria for statistical significance, pharmacokinetic feasibility, and clinical relevance. Within this broader pool, ten antidiabetic agents which demonstrated meaningful inverse signal strength were selected for in-depth analysis: dulaglutide (ROR 0.181, 95% CI 0.136–0.242), insulin lispro (ROR 0.206, 95% CI 0.161–0.263), insulin glargine (ROR 0.246, 95% CI 0.205–0.295), insulin (ROR 0.340, 95% CI 0.295–0.390), insulin aspart (ROR 0.349, 95% CI 0.267–0.455), empagliflozin (ROR 0.400, 95% CI 0.311–0.514), liraglutide (ROR 0.419, 95% CI 0.319–0.552), metformin (ROR 0.446, 95% CI 0.407–0.489), sitagliptin (ROR 0.460, 95% CI 0.376–0.563), and semaglutide (ROR 0.622, 95% CI 0.507–0.764). The subsequent literature review discussed relevant immunomodulatory and anti-inflammatory properties for each of these agents, providing a mechanistic rationale for their potential therapeutic role in IBD. Conclusions: This study identifies antidiabetic drugs as plausible repurposing candidates for IBD, supported by both pharmacovigilance-derived inverse signals and a body of mechanistic and clinical literature suggesting shared pathophysiological pathways between the two conditions. However, it should be acknowledged that the clinical evidence supporting the therapeutic efficacy of several candidates remains variable or incomplete, and robust interventional data are largely lacking. Ultimately, the findings of this study generate testable hypotheses and highlight a set of candidate therapies that warrant dedicated experimental and clinical investigation, including well-designed prospective trials, to determine their true therapeutic potential in IBD management. Full article

Metformin-associated lactic acidosis (MALA) involves mitochondrial Complex I inhibition, traditionally diagnosed via indirect markers. We present platelet high-resolution respirometry (HRR) as a novel “liquid biopsy” to directly quantify metformin-induced systemic bioenergetic lesions. A 65-year-old diabetic male presented with severe lactic acidosis, acute kidney injury, and profound hypoglycemia after intentionally overdosing on metformin (120 g), dapagliflozin (600 mg), and insulin glargine (300 U). While hemodialysis cleared plasma metformin and resolved the acidosis, refractory hypoglycemia required high-dose IV glucose for over six days. Day 2 platelet HRR revealed severe Complex I inhibition despite significantly decreased plasma metformin, indicating a profound “toxicodynamic lag.” Mitochondrial bioenergetics recovered by Day 7, reflecting natural platelet turnover. The protracted hypoglycemia was driven by a synergistic triad: metformin-inhibited gluconeogenesis, insulin glargine’s prolonged depot effect, and dapagliflozin-induced persistent renal glucose wasting. Platelet HRR has the potential to be a clinically applicable tool to reveal the “hidden” cellular phase of metformin toxicity missed by standard biomarkers. Furthermore, clinicians must anticipate severe, protracted hypoglycemia in mixed overdoses involving SGLT2 inhibitors. Full article

Background/Objectives: Insulin glargine U300 (IGlarU300) is a second-generation, long-acting insulin analog designed to provide a more stable pharmacokinetic profile compared to insulin glargine U100. However, long-term real-world data reflecting its long-term impact on glycemic control and hypoglycemia across diverse populations remain limited. This study evaluated the 24-month clinical outcomes of transitioning to IGlarU300 in a real-world setting. Methods: This retrospective, single-center, observational study enrolled patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) who transitioned to IGlarU300 between 2017 and 2021. HbA1c levels, body weight, insulin doses, and hypoglycemia rates were evaluated at baseline and up to 24 months. Results: A total of 242 patients (T1DM: n = 68, T2DM: n = 174) were analyzed. HbA1c levels significantly declined at all follow-up points compared to baseline (mean change at 12 months: −0.85% [95% CI: −1.24 to −0.47%]; p < 0.001]). No significant change in total insulin dose was observed over the one-year follow-up; however, improved glycemic control led to a significant reduction in oral antidiabetic medication use, reflecting successful treatment simplification and a decrease in polypharmacy burden (mean change: -0.50 [95% CI: −0.70 to −0.30]; p < 0.001). Notably, both severe and mild hypoglycemia episodes showed significant reductions (p = 0.010 and p = 0.019, respectively). Switching to IGlarU300 was associated with sustained improvements in glycemic control and a reduction in hypoglycemia rates. Conclusions: These findings suggest that IGlarU300 may be an effective clinical option for optimizing metabolic outcomes, though further controlled studies are warranted to confirm these observational results. Full article

Objective: To evaluate the efficacy of Roux-en-Y gastric bypass (RYGB) in improving glucose regulation and metabolic parameters in feline diabetes mellitus (FDM). Methods: FDM was experimentally induced via partial pancreatectomy, splenectomy, and dexamethasone administration. Following insulin stabilization, the RYGB cohort underwent gastric bypass, while the medical management group received glargine insulin. Untreated diabetic controls were monitored for 12 weeks. Blood glucose (GLU), fructosamine (FRU), biochemical profiles, and metabolic hormones were evaluated pre- and post-intervention. Hepatic and pancreatic tissues were collected for histopathological examination. Results: GLU and FRU concentrations in the RYGB group were significantly lower than in diabetic controls (p < 0.05), remaining comparable to the insulin-treated group (p > 0.05). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly reduced post-RYGB (p < 0.05), closely matching insulin therapy outcomes (p > 0.05). Hormonal assays demonstrated decreased gastric inhibitory polypeptide (GIP) and elevated glucagon-like peptide-1 (GLP-1) in RYGB cats. Histopathologically, the RYGB group exhibited attenuated hepatic steatosis and a higher density of pancreatic islet cells with abundant cytoplasm compared to the control groups. Conclusions: RYGB effectively restores glycemic control and metabolic hormone balance in FDM, promoting morphological improvements in pancreatic islets and offering a highly promising alternative therapy for diabetic felines. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance, impaired insulin secretion, and chronic hyperglycemia. Recent studies have identified microRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level, as modulators of pathways involved in T2DM pathophysiology. Dysregulated miRNA expression has been detected in various samples collected from patients with T2DM, implicating these molecules in disease onset and progression. Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published from the earliest available records to 18 August 2025 using the following Boolean search terms: “miRNA AND gliclazide”, “miRNA AND glibenclamide”, “miRNA AND gliquidone”, “miRNA AND glimepiride”, “mirRNA AND metformin”, “miRNA AND pioglitazone”, “miRNA AND rosiglitazone”, “miRNA AND sitagliptin”, “miRNA AND vildagliptin”, “miRNA AND alogliptin”, “miRNA and saxagliptin”, “miRNA AND linagliptin”, “miRNA AND liraglutide”, “miRNA and dulaglutide”, “miRNA AND semaglutide”, “miRNA AND tirzepatide”, “miRNA AND lixisenatide”, “miRNA AND empagliflozin”, “miRNA AND dapagliflozin”, miRNA AND insulin glargine”, “miRNA AND insulin detemir”, “miRNA AND insulin degludec”, “miRNA AND insulin aspart”, “miRNA AND insulin glulisine”, and “miRNA AND insulin lispro”. Additionally, gray literature was searched in ClinicalTrials.gov, the EU Clinical Trials Register (EudraCT), and the ISRCTN Registry to identify unpublished studies. Studies were eligible for inclusion if they were clinical interventional studies assessing the impact of currently available antidiabetic treatments on miRNA expression. Only articles published in English were considered. The risk of bias was evaluated using the RoB2 (Risk of Bias 2) and ROBINS-I (Risk Of Bias In Non-randomized Studies—of Interventions) tools. Study characteristics and major findings were tabulated. Results: A total of 1263 manuscripts was identified initially. After removing duplicates, 726 articles remained for further screening. Ultimately, 17 manuscripts reporting interventional clinical trials on the effects of antidiabetic treatment on miRNA were included, encompassing a total of 1093 patients. Key findings included treatment-associated changes in miRNA expression and their potential utility for the prediction of clinical outcomes. Conclusions: Current evidence supports the hypothesis that antidiabetic treatments modulate miRNA expression, with some findings showing predictive value for metabolic outcomes. However, the available data remain limited and of low grade of certainty, and further large-scale clinical studies are needed to provide deeper insights into these associations. Full article

Background/Objectives: Oral insulin continues to constitute a challenge due to its low uptake by the gut wall and degradation by gastrointestinal proteolytic enzymes. Such concerns might be surmounted by means of nanoparticle delivery. Methods: In this study, glargine insulin has been loaded into solid lipid nanoparticles prepared via coacervation from Shea and Mango soaps, due to hydrophobic ion pairing. Subsequently, ex vivo tied-up-gut experiments were performed with fluorescently labeled peptide. Additionally, re-dispersible oral solid dosage forms (powders and tablets) were obtained from nanoparticle suspensions via freeze-drying and spray-drying. Results: Solid lipid nanoparticles are capable of enhancing peptide permeation into different gut sections. Furthermore, spray-drying permits the preparation, which can be scaled up, of a re-dispersible powder from the nanoparticle suspension. Conclusions: This engineered process is suitable for the formulation of solid oral dosage forms, such as granulates and tablets, and presents promising potential for oral insulin delivery, paving the way for the assessment of its pharmacological efficacy in further in vivo studies. Full article

Background/Objectives: Long-acting insulin glargine (iGlar) has been available as a biosimilar since 2014 in the UK. We reviewed previous prescribing to evaluate if the anticipated cost savings with biosimilars were realized with iGlar. Methods: This study investigated prescribing patterns of long-acting iGlar (100 units/mL) in cartridges and pre-filled pens from 2020 to 2024 across primary care organizations in England, Northern Ireland, Scotland, and Wales. Results: iGlar prescribing declined in all of the four nations. From 2020 to 2024, the total prescribed quantity of biosimilars persistently increased in all countries, reaching 24% in England, 5% in Northern Ireland, 24% in Scotland, and 11% in Wales, all in 2024. Consequently, the proportion of Lantus prescriptions (as quantity) decreased but continued to exceed that of all available iGlar products combined in all countries in all years analyzed. By 2024, Lantus was also priced lower than the most common biosimilar, Abasaglar, across all nations. Conclusions: The introduction of biosimilars does not automatically result in altered prescribing practices, though we show that the most commonly prescribed iGlar was also the least expensive product at the end of the analysis period. At launch and for several years after, biosimilars failed to gain strong utilization, despite cost advantages, highlighting the need for active switching policies and prescriber engagement. Full article

The aim of this study was to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of two insulin glargine preparations in healthy Chinese male subjects. Methods: Forty healthy Chinese male subjects were enrolled in this randomized, open, two-sequence, four-period, single-dose, crossover study and were randomly divided into RTRT or TRTR (first-period injection of test preparation, second-period injection of reference preparation, third-period injection of test preparation, fourth-period injection of reference preparation) groups. A 24 h euglycemic clamp test measured GIR. Plasma insulin glargine concentration and C-peptide were collected during the trial and analyzed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). WinNonLin calculated PD/PK parameters and the equivalence of the two preparations was testified by SAS9.2. Results: The average concentration of C-peptide was lower than the baseline and the blood glucose was close to the targeted value in each sequence. PK parameters c_max of the test and the reference preparation insulin glargine were 0.580 and 0.614 ng·mL⁻¹, and the AUC_0–24h were 9.782 and 10.436 h·ng·mL⁻¹, respectively. PD parameters GIR_max were 42.748 and 45.279 mg·kg⁻¹·min⁻¹, and AUC_GIR,0–24h were 2.924 and 3.096 h·mg·kg⁻¹·min⁻¹, respectively. There was no clinically significant adverse reaction observed during the experiment. Conclusions: The glucose clamp has been established and bioequivalence between test preparation and reference preparation has been demonstrated. Full article

Background. One hundred years have passed since the discovery of insulin, which is one of the most relevant events of the 20th century. This period resulted in extraordinary progress in the development of novel molecules to improve glucose control, simplify the insulin regimen, and ameliorate the quality of life. In late March 2024, the first once-weekly basal analog Icodec was approved for diabetes mellitus, generating high expectations. Our aim was to systematically review and meta-analyze the efficacy and safety of Icodec compared to once-daily insulin analogs in type 1 (T1D) and type 2 diabetes (T2D). Methods. PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for randomized clinical trials (RCTs). Studies were included for the synthesis according to the following prespecified inclusion criteria: uncontrolled T1D or T2D, age ≥ 18 years, insulin Icodec vs. active comparators (Degludec U100, Glargine U100, Glargine U300, and Detemir), phase 3, multicenter, double-blind or open-label RCTs, and a study duration ≥ 24 weeks. Results. The systematic review included 4347 patients with T1D and T2D inadequately controlled (2172 randomized to Icodec vs. 2175 randomized to once-daily basal analogs). Icodec, compared to once-daily basal analogs, slightly reduced the levels of glycated hemoglobin (HbA1c) with an estimated treatment difference (ETD) of −0.14% [95%CI −0.25; −0.03], p = 0.01, and I² 68%. Patients randomized to Icodec compared to those on once-daily basal analogs had a greater probability to achieve HbA1c < 7% without clinically relevant or severe hypoglycemic events in 12 weeks from randomization with an estimated risk ratio (ERR) of 1.17, [95%CI 1.01, 1.36], p = 0.03, and I² 66%. We did not find a difference in fasting glucose levels, time in range, and time above range between Icodec and comparators. Icodec, compared to once-daily basal analogs, resulted in a slight but statistically significant weight gain of 0.62 kg [95%CI 0.25; 0.99], p = 0.001, and I² 25%. The frequency of hypoglycemic events (ERR 1.16 [95%CI 0.95; 1.41]), adverse events (ERR 1.04 [95%CI 1.00; 1.08]), injection-site reactions (ERR 1.08 [95%CI 0.62; 1.90]), and the discontinuation of treatments were similar between the two groups. Icodec was found to work better when used in a basal-only than basal-bolus regimen with an ETD in HbA1c of −0.22%, a probability of achieving glucose control of +33%, a probability of achieving glucose control without clinically relevant or severe hypoglycemia of +28%, more time spent in target (+4.55%) and less time spent in hyperglycemia (−5.14%). The risk of clinically relevant or severe hypoglycemic events was significantly higher when background glinides and sulfonylureas were added to basal analogs (ERR 1.42 [95%CI 1.05; 1.93]). Conclusion. Insulin Icodec is substantially non-inferior to once-daily insulin analogs in T2D, either insulin-naïve or insulin-treated. However, Icodec works slightly better than competitors when used in a basal-only rather than basal-bolus regimen. Weight gain and hypoglycemic risk are substantially low but not negligible. Patients’ education, adequate lifestyle and pharmacological interventions, and appropriate therapy adjustments are essential to minimize risks. This systematic review is registered as PROSPERO CRD42024568680. Full article

Background: A study to assess the glucose levels of people with type 1 diabetes (T1D) overnight, based on the insulin type and timing. Methods: A real-world, retrospective study of T1D, using multiple daily insulin injections. Continuous glucose monitoring and insulin injection data were collected for ten hours after dinner using the Insulclock^® connected cap. Meal events were identified using the ROC detection methodology. The timing of the rapid insulin, second injections, and the type of insulin analogs used, were evaluated. Results: The nocturnal profiles (n = 775, 49 subjects) were analyzed. A higher glucose AUC of over 180 mg/dL was observed in subjects with delayed injections (number; %; mg/dL × h): −45–15 min (n = 136; 17.5%, 175.9 ± 271.0); −15–0 min (n = 231; 29.8%, 164.0 ± 2 37.1); 0 + 45 min (n = 408; 52.6%, 203.6 ± 260.9), (p = 0.049). The use of ultrarapid insulin (FiAsp^®) (URI) vs. rapid insulin (RI) analogs was associated with less hypoglycemia events (7.1 vs. 13.6%; p = 0.005) and TBR70 (1.7 ± 6.9 vs. 4.6 ± 13.9%; p = 0.003). Users of glargine U300 vs. degludec had a higher TIR (70.7 vs. 58.5%) (adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n = 144, 18.6%) was associated with a higher number of hypoglycemia events (18.1 vs. 9.5%; p = 0.003), TBR70 (5.5 ± 14.2 vs. 3.0 ± 11.1%; p = 0.003), a glucose AUC of over 180 mg/dL (226.1 ± 257.8 vs. 178.0 ± 255.3 mg/dL × h; p = 0.001), and a lower TIR (56.0 ± 27.4 vs. 62.7 ± 29.6 mg/dL × h; p = 0.004). Conclusion: The dinner rapid insulin timing, insulin type, and the use of correction injections affect the nocturnal glucose profile in T1D. Full article

Background and Objectives: Degludec (Deg) and glargine U300 (Gla-300) are insulin analogs with longer and smoother pharmacodynamic action than glargine U100 (Gla-100), a long-acting insulin that has been widely used for many years in type 1 and type 2 diabetes. Both improve glycemic variability (GV) and the frequency of hypoglycemia, unlike Gla-100. However, it is unclear which insulin analog affects GV and hypoglycemia better in patients with insulin-dependent type 1 diabetes. We evaluated the effects of switching from Deg to Gla-300 on the day-to-day GV and the frequency of hypoglycemia in patients with insulin-dependent type 1 diabetes treated with Deg-containing basal-bolus insulin therapy (BBT). Materials and Methods: We conducted a retrospective study on 24 patients with insulin-dependent type 1 diabetes whose treatment was switched from Deg-containing BBT to Gla-300-containing BBT. We evaluated the day-to-day GV measured as the standard deviation of fasting blood glucose levels (SD-FBG) calculated by the self-monitoring of blood glucose records, the frequency of hypoglycemia (total, severe, and nocturnal), and blood glucose levels measured as fasting plasma glucose (FPG) levels and hemoglobin A1c (HbA1c). Results: The characteristics of the patients included in the analysis with high SD-FBG had frequent hypoglycemic events, despite the use of Deg-containing BBT. For this population, SD-FBG and the frequency of nocturnal hypoglycemia decreased after the switch from Deg to Gla-300. Despite the decrease in the frequency of nocturnal hypoglycemia, the FPG and HbA1c did not worsen by the switch. The change in the SD-FBG had a negative correlation with the SD-FBG at baseline and a positive correlation with serum albumin levels. Conclusions: Switching from Deg to Gla-300 improved the SD-FBG and decreased the frequency of nocturnal hypoglycemia in insulin-dependent type 1 diabetes treated with Deg-containing BBT, especially in cases with low serum albumin levels and a high GV. Full article

We described insulin glargine (originator) and insulin glargine-yfgn (biosimilar) treatment patterns, assessed effectiveness and safety outcomes, and identified reasons for switching back to the originator product from the biosimilar. This retrospective study included 328,463 Veterans 18 years of age and older who received one or more outpatient prescriptions for insulin glargine and/or insulin glargine-yfgn between 1 June 2021 and 31 December 2022. Patients were assigned to subgroups based on the initial prescription during the study period, prevalent versus incident use for originator insulin glargine, and prior versus no prior use of the originator before the biosimilar (i.e., prevalent originator non-switcher (n = 189,734), originator switch to biosimilar (n = 81,010), incident originator non-switcher (n = 49,401), and incident biosimilar (n = 8318)). There were no differences in the outcome of mean HbA1c (7.9% for all subgroups). There were also no differences in the unadjusted rates of hospitalization and/or emergency room visits for hyper- and hypoglycemia between the prevalent originator non-switcher and originator switched to biosimilar subgroups (p = 0.09 and 0.38, respectively) or the incident originator non-switcher and incident biosimilar subgroups (p = 0.054 and 0.61, respectively). Finally, none of the HbA1c or hyperglycemia outcomes adjusted for baseline characteristics were statistically different. Adjusted analyses for rates of hospitalization and/or emergency room visits for hypoglycemia could not be performed due to the low number of events. Overall, patients who received insulin glargine-yfgn had similar effectiveness and safety outcomes as patients who received the originator. Full article

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA_1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits. Full article

For the quantification of insulin activity, United States Pharmacopeia (USP) general chapter <121> continues to require the rabbit blood sugar test. For new insulin or insulin analogue compounds, those quantitative data are expected for stability or comparability studies. At Sanofi, many rabbits were used to fulfil the authority’s requirements to obtain quantitative insulin bioactivity data until the in vivo test was replaced. In order to demonstrate comparability between the in vivo and in vitro test systems, this study was designed to demonstrate equivalency. The measurement of insulin lispro and insulin glargine drug substance and drug product batches, including stress samples (diluted or after temperature stress of 30 min at 80 °C), revealed a clear correlation between the in vitro and in vivo test results. The recovery of quantitative in vitro in-cell Western (ICW) results compared to the in vivo test results was within the predefined acceptance limits of 80% to 125%. Thus, the in vitro ICW cell-based bioassay leads to results that are equivalent to the rabbit blood sugar test per USP <121>, and it is highly suitable for insulin activity quantification. For future development compounds, the in vitro in-cell Western cell-based assay can replace the rabbit blood sugar test required by USP <121>. Full article

Metabolic diseases are a worldwide health problem. Insulin resistance (IR) is their distinctive hallmark. For their study, animal models that provide reliable information are necessary, permitting the analysis of the cluster of abnormalities that conform to it, its progression, and time-dependent molecular modifications. We aimed to develop an IR model by exogenous insulin administration. The effective dose of insulin glargine to generate hyperinsulinemia but without hypoglycemia was established. Then, two groups (control and insulin) of male Wistar rats of 100 g weight were formed. The selected dose (4 U/kg) was administered for 15, 30, 45, and 60 days. Zoometry, a glucose tolerance test, insulin response, IR, and the serum lipid profile were assessed. We evaluated insulin signaling, glycogenesis and lipogenesis, redox balance, and inflammation in the liver. Results showed an impairment of glucose tolerance, dyslipidemia, hyperinsulinemia, and peripheral and time-dependent selective IR. At the hepatic level, insulin signaling was impaired, resulting in reduced hepatic glycogen levels and triglyceride accumulation, an increase in the ROS level with MAPK-ERK1/2 response, and mild pro-oxidative microenvironmental sustained by MT, GSH, and GR activity. Hepatic IR coincides with additions in MAPK-p38, NF-κB, and zoometric changes. In conclusion, daily insulin glargine administration generated a progressive IR model. At the hepatic level, the IR was combined with oxidative conditions but without inflammation. Full article