Zanosar (streptozocin) / Teva - LARVOL DELTA

Two unreported lecanoric acid derivatives isolated from Chaetomium globosum KM651986 and their anti-diabetic effect. (PubMed, Sci Rep) - "Consequently, the crude methanol extract of C. globosum, compounds 1 and 2 were investigated for their anti-diabetic activity using streptozocin (STZ) - induced diabetic rat model...Compound 2 also elevated hepatic G6PD, normalized cAMP levels, and decreased hepatic α-amylase, indicating its potential in improving glucose metabolism at the hepatic level. Therefore, compound 2 emerges as particularly promising anti-diabetic candidate meriting further investigation into its potential therapeutic mechanisms of action."

Journal • Diabetes

Effects of DA-9701 (motilitone®) on gastric emptying, glycemic control, and oxidative stress in diabetic rats. (PubMed, PLoS One) - "DA-9701 normalized gastric emptying and glycemic control while reducing the expression of ERK1/2, c-Kit, and PCNA, which are elevated in diabetic gastric tissues. These findings highlight the dual therapeutic potential of DA-9701 in regulating both gastrointestinal motility and glycemic variability in diabetes, warranting further investigation in clinical settings."

Journal • Preclinical • Diabetes • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • KIT • MAPK1 • MAPK3 • OGG1 • PCNA

Ablation of LAT2 Transporter Causes Intramuscular Glutamine Accumulation and Inhibition of Fasting-Induced Proteolysis. (PubMed, J Cachexia Sarcopenia Muscle) - "LAT2 has a critical role in regulating Gln efflux from skeletal muscle. The absence of LAT2 led to elevated intracellular Gln levels, impairing muscle proteolysis by inducing mTORC1 recruitment to the lysosome. Further, chronic Gln accumulation and decreased proteolysis were found to induce the early onset of an age-related muscle phenotype."

Journal • Cachexia • Cataract • Diabetes • Metabolic Disorders • Oncology • Ophthalmology • Otorhinolaryngology • Targeted Protein Degradation • Type 1 Diabetes Mellitus • LAMP1

Multidimensional Evaluation of the Streptozotocin-Induced Alzheimer's Model: Integrating Molecular, Histopathological, and Behavioral Correlates Over Time. (PubMed, Neurochem Res) - "Limitations such as lack of neurofibrillary tangles and sex evaluations require investigation. Studies exploring tau pathology, sex differences, and long-term dynamics may refine therapeutic strategies."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Oncology • BDNF • TNFA

Targeting Fyn Kinase for Alleviation of Cognitive Impairment in Streptozocin-Induced Alzheimer's Disease in Mice by Loperamide; An Experimental and in Silico Analysis. (PubMed, Neurochem Res) - No abstract available

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

FCGR2B knockdown alleviates diabetes-induced cognitive dysfunction by altering neuronal excitability. (PubMed, Mol Med) - "Knock-down FCGR2B within hippocampus of DM mice activated PI3K/AKT signaling pathway via SHC1 in DM mice and alleviated DM-induced cognition impairment. Knock-down FCGR2B alleviated DM-induced cognition impairment by regulating hippocampal neuronal excitability. Thus, this work suggested that FCGR2B may be a potential target for treatment of DM-induced cognitive dysfunction."

Journal • Alzheimer's Disease • Cognitive Disorders • Diabetes • Metabolic Disorders • FCGR2B • FOS

Dr James Yao @MDAndersonNews observes that, prior to 2011, the only FDA-approved systemic therapy for pancreatic neuroendocrine tumors was streptozocin! What a remarkable decade-plus of progress in the field and yet, for our patients, we have miles to go before we sleep …

Resveratrol ameliorates streptozotocin induced renal inflammation and promotes autophagy by mediating the SphK1 pathway via Sirt1 in Wistar rats. (PubMed, Food Chem Toxicol) - "Streptozocin (STZ) has toxic effects on pancreatic β-cells and induces diabetic nephropathy (DN)...Mechanistically, we believe this may be related to Sirt1 stably binding to SphK1, thereby reducing the enzymatic activity of SphK1. These findings showed that RSV attenuated renal inflammation and promoted autophagy in STZ-induced DN rats by mediating the SphK1 pathway via Sirt1, suggesting that RSV may be a potentially effective compound for delaying the development of DN."

Journal • Preclinical • Diabetic Nephropathy • Inflammation • Nephrology • Renal Disease • BECN1 • ICAM1 • SPHK1 • TGFB1

Comparative efficacy of systemic therapies in malignant insulinoma. (PubMed, Endocr Relat Cancer) - "The most commonly used therapies included somatostatin analogs (SSA), everolimus, capecitabine-temozolomide (CAPTEM), and peptide receptor radionuclide therapy (PRRT)...SSA, chemotherapy, and streptozocin were less effective, with hypoglycemic improvement seen in 37.5%, 33.3%, and 28.6% of patients, respectively...Cox regression analysis identified primary tumor resection and a history of benign insulinoma as associated with longer OS. Optimal sequencing of therapies remains unclear, and individualized treatment plans based on hypoglycemic burden and tumor characteristics are critical for improving survival and quality of life in these patients."

Journal • Endocrine Cancer • Hypoglycemia • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

Hypoglycemic episodes exacerbate skeletal muscle insulin resistance in type 2 diabetes mellitus. (PubMed, J Adv Pharm Technol Res) - "The study utilized 24 male rats (Rattus norvegicus) and the rates were categorized into the following groups: control (K1), streptozocin-induced diabetic without hypoglycemia (K2), streptozocin-induced diabetic with mild hypoglycemia (K3), and streptozocin-induced diabetic with severe hypoglycemia (K4)...Control group plasma levels were 2.48 ± 0.53 ng/ml for PGC-1α and 11.26 ± 1.21 ng/ml for Akt. Even mild episodes of hypoglycemia can lead to a substantial deterioration of insulin resistance in skeletal muscle."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Hyaluronan-based hydrogel achieves in situ administration of protocatechualdehyde to polarize macrophages to M2 phenotype for diabetic wound therapy. (PubMed, Int J Biol Macromol) - "When HA-PCAE was placed onto full-thickness wounds of mice with streptozocin-induced diabetes, it resulted in inflammation attenuation, vascular development, granulation tissue generation, and collagen deposition...Notably, HA-PCAE profoundly augmented diabetic wound recovery as compared with PCAE-loaded hydrogel formed using commercially available carboxymethylcellulose (INTRASITE Gel). This study reveals macrophage-modulatory capacity of PCAE, and demonstrates translational potential of HA-PCAE for diabetic wound treatment."

Journal • Diabetes • Inflammation • Metabolic Disorders

METRNL represses beta-to-alpha cell trans-differentiation to maintain beta cell function under diabetic metabolic stress in mice. (PubMed, Diabetologia) - "METRNL helps to maintain beta cell integrity, preventing beta-to-alpha cell trans-differentiation, and is necessary for beta cell compensation under metabolic stress, thereby inhibiting the progression of diabetes."

Journal • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • GCG • IRX2 • JUN • KLF6 • PDX1 • TFAM

AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity. (PubMed, bioRxiv) - "We observed that AMPK activation significantly reduced tumor formation in both diethylnitrosamine (DEN)-induced and streptozocin-induced (STAM) models of HCC. Our findings further implicate bile acid metabolism and hepatic nuclear factor alpha (HNF4α) signaling in the mechanism of AMPK-dependent HCC prevention. These findings provide mechanistic insights into AMPK biology and highlight the potential of AMPK as a therapeutic target, emphasizing the intricate interplay between metabolic dysregulation and cancer development."

Journal • Diabetes • Genetic Disorders • Hepatocellular Cancer • Metabolic Disorders • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus

Prevention of high-fat/high-sugar diet-induced type 2 diabetes mellitus-associated non-alcoholic fatty liver disease in rats with fermented and raw Rosa roxburghii Tratt (Cili) juice. (PubMed, Front Nutr) - "To compare and confirm the potential effects of spontaneous fermented/raw Cili juice (FCJ/RCJ) on type 2 diabetes mellitus (T2DM), the constituents of FCJ and RCJ were characterized and compared, high-fat/high-sugar diet (HFD) and streptozocin (STZ)-induced T2DM-associated non-alcoholic fatty liver disease (NAFLD) model rats were gavaged with FCJ/RCJ (1.5 mL/kg/day) for 20 weeks, after which serum, urine and liver and pancreas tissues were collected for experiments, and urine non-targeted metabolomics and liver transcriptomics analyses were conducted, and enhanced analysis of metabolomics results and the liver transcriptome...Notably, FCJ has a stronger anti-inflammatory effect, whereas RCJ preferentially regulates bile acid homeostasis and mitochondrial β-oxidation. The in vivo experiments of T2DM-associated NAFLD rats conducted in this study demonstrate that FCJ/RCJ has the potential to ameliorate metabolic disorders."

Journal • Preclinical • Diabetes • Dyslipidemia • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Collagen mimetic peptides as novel therapeutics for vascular disease in the central nervous system. (PubMed, Front Neurosci) - "We induced hyperglycemia in ApoE-deficient (ApoE-/-) mice by intraperitoneal injection of streptozocin (STZ; 50 mg/Kg) for 5 days and accelerated diabetic atherosclerotic disease through a high fat diet (HFD)...Application of CMP which intercalates with and repairs damaged collagen may have therapeutic use in neurodegenerative diseases by preserving vasculature structure and promoting blood-brain barrier integrity. These findings underscore the need to further explore the role of collagen repair as a novel therapeutic for diseases of the brain involving vascular degradation."

Journal • Atherosclerosis • Cardiovascular • CNS Disorders • Diabetes • Metabolic Disorders • Vascular Neurology • APOE • CD31 • PECAM1

Endothelial βII spectrin modulates ischemic-diabetic skin wound healing via regulating inflammation (SID 2025) - "We generated Sptbn1 endothelial specific conditional knockout (Sptbn1ECKO) mice and used a well-established mouse streptozocin-induced diabetic excisional dorsal wound model to study the function of SPTBN1 in diabetic wound healing...Sptbn1ECKO wounds also had significantly lower numbers of fibroblasts in the wound beds in the regenerative phase. Taken together, manipulating βII spectrin in endothelial cells may help understand the healing of chronic diabetic wounds and open doors for future research."

Inflammation • Metabolic Disorders • SMAD3 • TGFB1

Signal peptide-CUB-EGF domain-containing protein 1 levels in type 1 diabetes, type 2 diabetes, and obesity. (PubMed, Endokrynol Pol) - "The expression of SCUBE1 in both endothelial cells and platelets suggests that SCUBE1 could be used as a marker of endothelial dysfunction and platelet hyperactivity, which are significant complications in obesity, T1DM, and T2DM."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus • CASP3 • EGF • IFNG • IL6 • SCUBE1

Vaccinium myrtillus L. ameliorates diabetic nephropathy via modulating metabolites and gut microbiota in rats. (PubMed, Front Pharmacol) - "Streptozocin (STZ) combined with high fat induced DN model was established in rats...In addition, pretreatment with serum metabolite uridine also reduced the expression of LDH and mitochondrial ROS, and inhibited cell apoptosis. Our findings suggest that the improvement of gut microbiota and metabolic function were related to the anti-DN potential of VCE, and the underlying mechanism may be related to the inhibition of MAPK/NF-κB signaling pathway."

Journal • Preclinical • Diabetes • Diabetic Nephropathy • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • IL6 • TNFA

Multigenerational consequences of maternal high fat diet and gestational diabetes (GDM) at the preimplantation embryo stage (PAS 2025) - "On embryonic day (E)14, a subset of HF-fed rats was given streptozocin (STZ) to induce diabetes which was treated with insulin... Although F2e had no difference in expression of mitochondrial genes compared to controls (Ce), F3e, which had no direct exposure, had higher mitochondrial gene expression compared to both Ce and F2e (p < 0.05) (Fig1). Increased mitochondria quantity was validated by more staining compared to Ce (p < 0.01) (Fig 1). F2e had increased expression of genes activated during oxidative stress (p < 0.001) and more staining of reactive oxygen species (ROS) (p < 0.01) compared to Ce (Fig 2)."

Cardiomyopathy • Cardiovascular • Diabetes • Gestational Diabetes • Heart Failure • Metabolic Disorders

Grifola frondosa Polysaccharide F2 Ameliorates Disordered Glucose and Lipid Metabolism in Prediabetic Mice by Modulating Bile Acids. (PubMed, Foods) - "Our team previously reported that the Grifola frondosa (maitake mushroom) polysaccharide F2 reduced insulin resistance in T2DM rats induced by streptozocin (STZ) combined with a high-fat diet (HFD)...The results of 16S rDNA sequencing of feces from pre-DM mice showed that bile salt hydrolase (BSH)-producing bacteria, including Bacillus, Bifidobacterium, and Lactococcus, may be the therapy targets of F2 in pre-DM mice. Through the integrated analysis of untargeted metabolomics and 16S rDNA sequencing, it was found that F2 may ameliorate glucose and lipid metabolism disorders by promoting bile acid metabolism while regulating the abundance of BSH-producing bacteria (Lactococcus spp.), suggesting its potential as a functional food ingredient for the prevention of T2DM."

Journal • Preclinical • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Synergistic action of non-digestible xylooligosaccharide and Lactiplantibacillus plantarum ZDY2013 against high fat diet and streptozocin-induced type 2 diabetes mellitus in rats. (PubMed, Microbiol Res) - "Collectively, these findings suggest the potential use of synbiotics as a clinical intervention to ameliorate T2DM. This study provides a rationale for exploring dietary approaches as a mitigating strategy for managing long-standing diabetes."

Journal • Preclinical • Diabetes • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Type 2 Diabetes Mellitus

miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease. (PubMed, Ren Fail) - "DKD mice were established by intraperitoneally injecting streptozocin (STZ), and a DKD cell model was generated by culturing in media supplemented with 25 mmol/L glucose (high glucose, HG)...Furthermore, the miR-1225-3p inhibitor inhibited fibrosis and inflammation in the renal tissues of DKD mice. miR-1225-3p facilitates fibrosis and oxidative stress by mediating ARHGAP5/SMURF2-mediated ubiquitination of ChREBP."

Journal • Diabetes • Diabetic Nephropathy • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Targeted Protein Degradation • ARHGAP5 • MIR122 • SMURF2

Diabetic wound healing breakthrough: theaflavin-3, 3'-digallate nanoparticles@hydrogel activates the TGF-β1/SMAD3 pathway. (PubMed, Phytomedicine) - "TFDG NPS and TFDG NPS@hydrogel promoted wound closure in diabetic mice through the TFG-β1/SMAD3 pathway, thus exhibiting promising therapeutic potential for diabetic wound treatment."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • SMAD3 • TGFB1

Metformin attenuates diabetic osteoporosis by suppressing ferroptosis via the AMPK/Nrf2 pathway. (PubMed, Front Pharmacol) - "In vivo, we developed a DOP model utilizing a high-fat diet along with streptozocin injections and evaluated the bone-protective effects of Met through micro-CT and histomorphological analyses. Additionally, in vivo results demonstrated Met alleviates bone loss and microstructural deterioration in DOP rats. Met can activate the AMPK/Nrf2 pathway to prevent ferroptosis, thereby protecting against DOP."

Journal • Diabetes • Osteoporosis • Rheumatology • COL1A1 • GPX4 • RUNX2

Alleviation of nephropathy during aging as complications of diabetic by natural products. (PubMed, Afr Health Sci) - "The study included 60 male albino rats sorted into five groups: GP (I): control and the other rat groups were induced diabetic by a single dose of streptozocine i.p, at dose of (55 mg/kg/b.w).GP II was considered as diabetic untreated...Data obtained revealed that, diabetic rats treated with anserine or α-tocopherol or combination improve abnormalities, glucose, HA1c, antioxidant enzymes, inflammatory mediators and AGEs versus untreated diabetic. Dietary supplement of natural products as anserine and α-tocopherol protect against micro and microvascular system, which is suggestive as alternative or complementary therapeutic agents for diabetic complications as neuropathy, nephropathy, and CVD."

Journal • Diabetes • Diabetic Nephropathy • Diabetic Neuropathy • Inflammation • Nephrology • Pain • Renal Disease • IL6 • TNFA