Insulin (human)

Insulin (human) is a peptide hormone that promotes glycogen synthesis and regulates glucose levels in the blood. Insulin (human) has hypoglycemic activity and is used clinically to treat hyperglycemia in diabetic patients.

Pioglitazone (U 72107) is a PPARγ agonist with EC50 of 0.93 and 0.99 μM on human and mouse PPARγ, respectively, and has selective and oral activity. Pioglitazone can be used in diabetes research.

GIP (3-42), human (Gastric Inhibitory Polypeptide (3-42) (human)) is a peptide that acts as a glucose-dependent proinsulinotropic polypeptide (GIP) receptor antagonist and regulates insulin secretion and the metabolic effects of GIP in vivo, which can be used to study type 2 diabetes.

OSI-906 (Linsitinib (OSI-906)) is an orally bioavailable small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Linsitinib selectively inhibits IGF-1R, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Overexpressed in a variety of human cancers, IGF-1R stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis.

HNMPA is a membrane impermeable inhibitor of insulin receptor tyrosine kinase. HNMPA inhibits tyrosine and serine autophosphorylation by the human insulin receptor. HNMPA exhibits no effect on cyclic AMP-dependent protein kinase or protein kinase C activities.

KW-2450 free base is an orally bioavailable inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) tyrosine kinases with potential antineoplastic activity. IGF-1R/IR inhibitor KW-2450 free base selectively binds to and inhibits the activities of IGF-1R and IR, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-R1 and IR tyrosine kinases, overexpressed in a variety of human cancers, play significant roles in the stimulation of cellular proliferation, oncogenic transformation, and suppression of apoptosis.

JBSNF-000028 is an orally active and potent nicotinamide N-methyltransferase (NNMT) inhibitor with inhibitory effects on human NNMT (hNNMT), monkey NNMT (mkNNMT), and mouse NNMT (mNNMT) with IC50s of 0.033 μM, 0.19 μM, and 0.21 μM, respectively.JBSNF-000028 can drive insulin sensitization and weight loss. 000028 drives insulin sensitization, glucose regulation and weight loss and can be used to study metabolic disorders.

β-Aminopropionitrile (3-Aminopropionitrile) is a selective inhibitor of lysyl oxidase.

Butanoic acid is an endogenous human metabolite, an endogenous histone deacetylase (HDAC) inhibitor. The IC50 of HDAC3, HDAC4 and HDAC1 were 2.4 mM, 4.5 mM and 5.3 mM, respectively. 3-Hydroxybutyric acid has the effects of energy metabolism, neuroprotection, anti-inflammatory, and improvement of insulin resistance.

Cyclohexane-1,2,3,4,5,6-hexaol, also known as inositol, is a natural cyclohexane derivative and alcohol compound with biological activity in signal transduction, osmotic pressure regulation, and lipid metabolism, and is widely used in biochemical experiments and drug synthesis research.

Temocapril is an inhibitor of tyrosine kinase.

SBI-477 is a chemical probe that stimulates insulin signaling by deactivating the transcription factor MondoA. It coordinately inhibits triacylglyceride (TAG) synthesis and enhances basal glucose uptake in human skeletal myocytes.

D5D-IN-326 is an orally active delta-5 desaturase (D5D) inhibitor (IC50s: 72 and 22 nM for rat and human D5D in enzymic and cell-based assays). It has no effect on D6D or D9D activity. D5D-IN-326 reduces insulin resistance and decreases body weight in die

KGA-2727 is a potent and selective SGLT1 inhibitor, with Kis of 97.4 nM and 43.5 nM for human and rat SGLT1, respectively. The selectivity ratios (Ki for SGLT2/Ki for SGLT1) of KGA-2727 are 140 (human) and 390 (rat). KGA-2727 for the treatment of diabete.

LY2922470 reduces glucose levels along with significant enhancements in insulin and GLP-1, which is the potential for the treatment of type 2 diabetes mellitus (T2DM). LY2922470 is an effective, selective, and orally available agonist of the G protein-cou

ZIGIR enables insulin content-based separation of heterogeneous beta cells and islet sorting into pure alpha and beta cells, revealing unexpected zinc(II) activity in somatostatin granules of delta cells in human islets.

ZP3022 is a dual agonist targeting the glucagon-like peptide 1 receptor (GLP-1R) and cholecystokinin 2 (CCK2) receptor. It selectively enhances cAMP accumulation or ERK phosphorylation in HEK293 cells with GLP-1R or CCK2 receptor expression, compared to ERK phosphorylation in cells with the CCK1 receptor (EC50s: 0.02, 10.3, and >1,000 nM for human receptors, respectively). At 40 nM, ZP3022 promotes proliferation of rat neonatal β-cells in vitro. It also boosts glucose-induced insulin secretion (GSIS) in rat pancreatic islets at 10 and 100 nM concentrations and decreases body weight in rats at 40 nmol/kg doses twice daily. Administered at 100 nmol/kg daily, ZP3022 enhances β-cell and total pancreatic mass and improves glucose tolerance in db/db mice, while reducing food intake but not body weight in these mice.

NVP-DPP728 is a potent, reversible, nitrile-dependent inhibitor of dipeptidyl peptidase IV (DPP-IV) with an inhibition constant (K i) of 11 nM for human DPP-IV amidolytic activity. By inhibiting the degradation of glucagon-like peptide-1 (GLP-1), NVP-DPP728 enhances insulin release following glucose intake, making it useful for diabetes research [1].

AZD6482 (S-isomer) is a potent, selective, ATP-competitive PI3Kβ inhibitor (IC(50) 0.01 μm), which can inhibit insulin-induced in vitro glucose uptake by human adipocytes (IC(50) is 4.4 μm).

Ganglioside GM3 is a monosialoganglioside that demonstrates antiproliferative and proapoptotic effects in tumor cells by modulating cell adhesion, proliferation, and differentiation. It suppresses angiogenesis and reduces proliferation and migration of human umbilical vein endothelial cells (HUVECs) when used at a concentration of 20 μM via inhibition of VEGFR2 and Akt phosphorylation. Ganglioside GM3 induces dissociation of the insulin receptor-caveolin-1 complex from lipid microdomains, functioning as an inhibitor of insulin signaling and contributing to insulin resistance in adipocytes. Ganglioside GM3 mixture contains ganglioside GM3 molecular species with C18:1 and C20:1 fatty acyl chains.

Neuromedin U (NMU) is a neuropeptide first demonstrated to drive smooth muscle contraction.1Translated as a 174 amino acid propeptide, NMU is cleaved to different lengths in different animals. It has diverse receptor-mediated rolesin vivo, as it regulates feeding, vasoconstriction, nociception, and bone remodeling and contributes to obesity, cancer and septic shock.2,2NMU-25 is the active form of NMU in humans. It binds with high affinity to receptors on human left ventricle and coronary artery (KDs = 0.26 and 0.11 nM, respectively), eliciting endothelium-independent vasoconstriction.3NMU-25 also suppresses glucose-stimulated insulin secretion in human islets, and this effect is lost in NMU R165W mutants, resulting in early-onset obesity.4 1.Mitchell, J.D., Maguire, J.J., and Davenport, A.P.Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBritish Journal of Pharmacology15887-103(2009) 2.Greenwood, H.C., Bloom, S.R., and Murphy, K.G.Peptides and their potential role in the treatment of diabetes and obesityRev.Diabet.Stud.8(3)355-368(2011) 3.Mitchell, J.D., Maguire, J.J., Kuc, R.E., et al.Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular systemCardiovascular Research81353-361(2009) 4.Alfa, R.W., Park, S., Skelly, K.R., et al.Suppression of insulin production and secretion by a decretin hormoneCell Metabolism21(2)323-333(2015)

Osteocalcin (1-49) is a non-collagenous peptide that is secreted by osteoblasts and odontoblasts and comprises 1-2% of the total protein in bone. Secretion of osteocalcin (1-49) is stimulated by 1,25-dihydroxy vitamin D and plasma levels increase in diseases that induce dysregulated bone turnover such as osteoporosis, Paget's disease, and primary hyperparathyroidism. Osteocalcin (1-49) is positively correlated with insulin sensitivity and negatively correlated with high blood glucose levels in women. In vitro, osteocalcin induces chemotaxis of MDA-MB-231 breast cancer cells, human peripheral blood monocytes, and rat osteosarcoma cells with osteoblast-like characteristics. It is also expressed by vascular smooth muscle cells (VSMCs) displaying an osteoblast-like phenotype and has been positively associated with calcification of aortic tissue and heart valves in humans.

FKGK 18 is an inhibitor of group VIA (GVIA) calcium-independent phospholipase A2 (iPLA2). It inhibits GVIA iPLA2 by 99.9% at 0.091 mole fraction in a mixed micelle activity assay and is selective for GVIA iPLA2 over GIVA cPLA2 and GV sPLA2 where it shows 80.8 and 36.8% inhibition, respectively. FKGK 18 inhibits iPLA2β activity in cytosolic extracts from INS-1 cells overexpressing iPLA2β (IC50 = ~50 nM) as well as iPLA2γ activity in mouse heart membrane fractions (IC50s = ~1-3 μM). It inhibits glucose-induced increases in prostaglandin E2 production and insulin secretion in human pancreatic islets when used at a concentration of 10 μM and inhibits thapsigargin-induced apoptosis in INS-1 cells overexpressing iPLA2β in a concentration-dependent manner. FKGK 18 (20 mg/kg, 3 times per week) reduces blood glucose levels in an intraperitoneal glucose tolerance test, decreases the incidence of diabetes, and increases serum insulin levels in non-obese diabetic (NOD) mice.

Obestatin is a 23 amino acid peptide hormone with a conserved C-terminal glycine residue and amidation site that is formed by cleavage of the ghrelin and obestatin prepropeptide.1It binds to the orphan receptor GPR39 (Kd= 1 nM) and stimulates cAMP production in CHO and HEK293 cells overexpressing human GPR39. Obestatin inhibits contraction of isolated mouse jejunum muscle strips induced by ghrelin .In vivo, obestatin (12.5-1,000 nmol/kg) suppresses food intake in a time- and dose-dependent manner and reduces body weight gain and gastric emptying in mice. Obestatin (0.22 g per animal) also reduces food intake and glucose response without affecting plasma insulin responses in fasted high-fat diet fed mice.2 1.Zhang, J.V., Ren, P.C., Avsian-Kretchmer, O., et al.Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intakeScience310(5750)996-999(2005) 2.Subasinghage, A.P., Green, B.D., Flatt, P.R., et al.Metabolic and structural properties of human obestatin {1-23} and two fragment peptidesPeptides31(9)1697-1705(2010)