Pioglitazone

Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Activation

This compound's principal molecular target is the peroxisome proliferator-activated receptor gamma (PPARγ) drugbank.compatsnap.comhellobio.comfrontiersin.orgmdpi.combiorxiv.org. The binding of this compound to PPARγ induces a crucial conformational change within its ligand-binding domain, which is essential for the receptor's activation biorxiv.orgjacc.org. This conformational alteration facilitates the dissociation of corepressor proteins and promotes the subsequent recruitment of coactivator proteins, thereby initiating the transcriptional machinery biorxiv.orgjacc.org. This compound is characterized as a potent and highly selective agonist for PPARγ mims.comhellobio.commdpi.com.

PPARγ exists in two primary isoforms, PPARγ1 and PPARγ2, which originate from alternative splicing and distinct promoter usage oup.comphysiology.org. PPARγ1 is widely distributed and expressed across numerous tissues, including the heart, skeletal muscle, kidney, pancreas, and various epithelial tissues researchgate.netoup.com. In contrast, PPARγ2 demonstrates a more restricted expression pattern, being predominantly found in adipose tissue researchgate.netoup.comphysiology.org. Despite these differences in tissue distribution and the presence of an additional 28 to 30 amino acids at the N-terminal of PPARγ2 compared to PPARγ1, experimental studies have indicated that both murine PPARγ1 and PPARγ2 respond to this compound with comparable half-maximal effective concentrations of activation frontiersin.orgoup.com. Furthermore, this compound exhibits a high affinity for both PPARγ1 and PPARγ2 nih.gov.

The activation of PPARγ by this compound leads to a substantial increase in the transcription of insulin-responsive genes, which are pivotal for regulating glucose and lipid production, transport, and utilization drugbank.compatsnap.comdiabetesonthenet.comresearchgate.netmdpi.com. This profound transcriptional modulation underlies this compound's capacity to enhance insulin sensitivity drugbank.compatsnap.comdiabetesonthenet.com.

Specific genes whose expression is notably influenced by this compound-mediated PPARγ activation include:

Glucose Transporter Type 4 (GLUT4): this compound enhances the expression of GLUT4 on the cell surface, thereby facilitating increased glucose uptake into muscle and adipose tissue cells patsnap.comnih.govphysiology.org.

Genes involved in gluconeogenesis: this compound diminishes hepatic glucose production by downregulating the expression of genes associated with gluconeogenesis in the liver patsnap.comdiabetesonthenet.com.

Genes related to lipid metabolism and storage: This category encompasses genes for fatty acid transporter protein, lipoprotein lipase (LPL), fatty acid synthase (FAS), acetyl-CoA synthetase (ACS), glycerol-3-phosphate dehydrogenase (GPDH), and glucokinase nih.govresearchgate.netdiabetesjournals.org. The activation of PPARγ promotes increased glucose uptake by adipocytes, which is subsequently incorporated into triglycerides for storage diabetesjournals.org.

Research findings from studies examining the effect of this compound on the mRNA levels of genes involved in glycerol-3-phosphate synthesis in subcutaneous fat from individuals with type 2 diabetes illustrate this transcriptional modulation researchgate.net:

The mRNA levels of other key lipogenic genes such as FAS, GPDH, and ACS have also been found to be highly correlated with PPARγ expression and increased upon this compound treatment, suggesting a coordinated transcriptional control system for these genes researchgate.netdiabetesjournals.org.

For PPARγ to effectively execute its transcriptional activation functions, it forms an obligate heterodimer with one of the Retinoid X Receptor (RXR) isoforms, which include RXRα, RXRβ, and RXRγ frontiersin.orgmdpi.comnih.govfrontiersin.orgjci.orgresearchgate.net. This PPARγ/RXR heterodimeric complex subsequently binds to specific DNA sequences known as peroxisome proliferator response elements (PPREs) located within the promoter regions of target genes frontiersin.orgmdpi.comnih.govfrontiersin.orgresearchgate.netfrontiersin.org. This binding event is a critical step in initiating the transcription of genes involved in various metabolic processes, including glucose and lipid metabolism mdpi.com.

Transcriptional Modulation of Insulin-Responsive Genes

Peroxisome Proliferator-Activated Receptor Alpha (PPARα) Modulation

While this compound is predominantly recognized for its agonism of PPARγ, it also functions as a weak agonist of human peroxisome proliferator-activated receptor alpha (PPARα) wikipedia.orgresearchgate.netfrontiersin.orgjacc.orgnih.gov. This modulation of PPARα contributes to additional pharmacological effects, particularly in the regulation of inflammatory responses jacc.orgnih.gov. Research indicates that this compound can repress endothelial TNFα-induced vascular cell adhesion molecule-1 (VCAM-1) mRNA expression and induce hepatic IκBα expression in a PPARα-dependent manner researchgate.netjacc.orgnih.govmedrxiv.org. These anti-inflammatory effects mediated through PPARα are observed most notably in endothelial cells jacc.orgnih.gov. It is important to note that the binding affinity and efficacy of this compound for PPARα are significantly lower when compared to its binding to PPARγ researchgate.net.

Other Potential Molecular Targets (e.g., Amine Oxidase [flavin-containing] B)

Beyond its well-established interactions with the PPAR family, this compound has been identified as a specific and reversible inhibitor of human amine oxidase [flavin-containing] B (MAO-B) drugbank.comdrugbank.commdpi.comacs.orgnih.govresearchgate.net. MAO-B is a flavin-dependent mitochondrial enzyme responsible for the oxidative deamination of certain amine-containing neurotransmitters mdpi.comnih.gov. Structural analysis of the enzyme-inhibitor complex has shown that the R-enantiomer of this compound binds within both the substrate and entrance cavities of the MAO-B active site, forming non-covalent interactions with surrounding amino acid residues drugbank.commdpi.comacs.orgnih.govresearchgate.net. This distinct binding mechanism differentiates this compound from many conventional MAO inhibitors, which often act via covalent inhibition and may not exhibit the same degree of isoenzyme selectivity drugbank.comacs.org. This inhibitory effect on MAO-B suggests potential neuroprotective properties for this compound, a mechanism that has been investigated in the context of neurodegenerative conditions such as Parkinson's disease drugbank.commdpi.comacs.orgnih.gov.

Enhanced Insulin Signaling and Glucose Disposal

This compound significantly enhances tissue sensitivity to insulin, leading to improved glucose uptake and utilization in peripheral tissues, including skeletal muscle and adipose tissue. drugbank.comresearchgate.netmyendoconsult.comtohoku.ac.jppharmacytimes.com This improvement in insulin sensitivity is a cornerstone of its action, as it allows for better clearance of glucose from the bloodstream without increasing pancreatic insulin secretion. drugbank.comresearchgate.nettohoku.ac.jp Studies have shown that this compound can increase insulin-stimulated glucose disposal by 25–56%. oup.com For instance, a 16-week this compound treatment in type 2 diabetic patients resulted in a 38% increase in insulin-stimulated total glucose disposal during high-dose insulin clamps. diabetesjournals.org This enhancement in glucose disposal contributes to lower plasma glucose and HbA1c levels. drugbank.comnih.gov

Table 1: Effects of this compound on Glucose Parameters in Type 2 Diabetic Patients (Mean Changes After Treatment) diabetesjournals.orgnih.gov

Reduction of Hepatic Gluconeogenesis

This compound reduces the hepatic production of glucose, a process known as gluconeogenesis. drugbank.comresearchgate.net This effect is crucial in mitigating fasting hyperglycemia, as the liver is a major site of glucose overproduction in individuals with type 2 diabetes. myendoconsult.comdiabetesjournals.org Research indicates that this compound significantly reduces the fasting rate of gluconeogenesis, and this decrease correlates with a decline in fasting plasma glucose concentrations. diabetesjournals.org This reduction in gluconeogenic flux is considered a strong determinant of this compound's antihyperglycemic effect. diabetesjournals.org

Regulation of Glucose Transporters (GLUT1, GLUT4)

This compound has been shown to increase the expression of glucose transporters, particularly GLUT1 and GLUT4. researchgate.netpharmacytimes.comnih.govthieme-connect.compsu.edu GLUT1 is important for basal glucose uptake, while GLUT4 plays a critical role in insulin-mediated glucose uptake in insulin-sensitive tissues like adipocytes and skeletal muscle. pharmacytimes.comnih.govomicsonline.orgnih.gov In studies involving 3T3-F442A cells, this compound treatment led to significant increases in GLUT1 and GLUT4 mRNA abundance (up to 5-fold) and protein levels (up to 10-fold for GLUT1 and 7-fold for GLUT4). nih.gov This enhancement in transporter expression is largely attributed to the stabilization of their messenger RNA transcripts. nih.gov By increasing the presence of these transporters, this compound facilitates glucose uptake into cells, thus improving glucose utilization and storage. myendoconsult.comnih.gov Interestingly, while this compound increases GLUT1 and GLUT4 expression, studies in human muscle have shown that this compound can reverse the overexpression of GLUT5 (a fructose transporter) observed in diabetic muscle, although the role of this effect in insulin sensitization is not fully clear. diabetesjournals.org

Modulation of Lipid Metabolism

This compound reduces plasma free fatty acid (FFA) levels. researchgate.netoup.comdiabetesjournals.orgthieme-connect.comnih.gov Elevated FFA levels are known to contribute to insulin resistance by stimulating gluconeogenesis and impairing hepatic glucose production. diabetesjournals.org By lowering circulating FFA concentrations, this compound indirectly improves insulin sensitivity and glucose metabolism. nih.govnps.org.au This reduction in FFAs can be attributed to increased fatty acid uptake and storage in adipocytes, thereby redirecting lipid burden away from the liver and muscle. nih.govnps.org.au Studies have reported significant decreases in fasting plasma FFA concentration following this compound treatment, for example, from 647 ± 39 μEq/l to 478 ± 49 μEq/l after 16 weeks. diabetesjournals.org

This compound demonstrates favorable effects on the lipid profile by significantly reducing plasma triglyceride (TG) levels and increasing high-density lipoprotein cholesterol (HDL-C) levels. researchgate.netpharmgkb.orgmyendoconsult.comtohoku.ac.jpsochob.clnih.govdiabetesjournals.orgresearchgate.netscispace.com Clinical trials have consistently shown a reduction in plasma triglycerides by 10–25% and an increase in total HDL-C levels by 10–20%, predominantly due to an increase in the larger HDL2 subfraction. sochob.clresearchgate.net For instance, one study reported a decrease in triglycerides from 219.2 ± 34.4 mg/dl to 189.2 ± 33.7 mg/dl, and an increase in HDL-C from 37.2 ± 2.9 to 41.5 ± 3.1 mg/dl. scispace.com Furthermore, this compound has been observed to reduce levels of small dense LDL particles while increasing levels of larger, less atherogenic LDL fractions. sochob.cldiabetesjournals.orgresearchgate.net This beneficial impact on lipid profiles is a critical aspect of this compound's mechanism, contributing to the management of diabetic dyslipidemia. sochob.clnih.govdiabetesjournals.org

Table 2: Changes in Lipid Parameters with this compound Treatment diabetesjournals.orgscispace.com

The Chemical Compound this compound: Mechanisms of Action and Biological Effects

This compound, a member of the thiazolidinedione (TZD) class of compounds, is a synthetic ligand for peroxisome proliferator-activated receptor-gamma (PPARγ). Its biological effects are primarily mediated through the activation of this nuclear receptor, which plays a crucial role in regulating glucose and lipid homeostasis. Beyond its well-established metabolic actions, this compound exhibits significant anti-inflammatory and immunomodulatory properties, as well as influences mitochondrial function.

This compound acts as a selective agonist at PPARγ, a nuclear receptor highly expressed in insulin-sensitive tissues such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ by this compound leads to changes in the transcription of insulin-responsive genes, thereby influencing glucose and lipid metabolism, transport, and utilization drugbank.comnih.gov. This mechanism contributes to enhanced tissue sensitivity to insulin and a reduction in hepatic glucose production (gluconeogenesis), leading to improved insulin resistance without increasing pancreatic beta cell insulin secretion drugbank.com.

Adipose Tissue Remodeling and Adipocyte Differentiation

This compound's molecular effects are largely attributed to its PPARγ-mediated regulation of adipocyte differentiation and lipid storage, particularly in adipose tissue where PPARγ is highly abundant nih.gov. The compound promotes the differentiation of preadipocytes into mature adipocytes, leading to an increase in the number of smaller, insulin-sensitive adipocytes diabetesjournals.orgresearchgate.netoup.com. This process, known as adipogenesis or hyperplasia, contributes to the beneficial remodeling of adipose tissue by expanding subcutaneous adipose depots and reducing ectopic and visceral fat accumulation nih.govdiabetesjournals.orgoup.com. The increase in smaller adipocytes with higher lipid storage potential is believed to lower circulating free fatty acid levels, which can improve insulin sensitivity in other tissues like skeletal muscle diabetesjournals.org. Studies have identified four distinct sub-distributions of adipocytes in human abdominal subcutaneous adipose tissue: small (~0.02uL), medium (~0.14uL), large (~0.9uL), and very large (~2.5uL) researchgate.net. This compound treatment has been shown to increase the proportion of small adipocytes while decreasing the area under the curve (AUC) for large adipocytes researchgate.net.

Table 1: Adipocyte Size Distributions and this compound's Effects

Influence on Sterol Regulatory Element-Binding Protein-1c (SREBP-1c)

Sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor that plays a critical role in regulating lipogenic gene expression and fatty acid biosynthesis researchgate.netnih.gov. This compound has been shown to reduce the expression of genes involved in hepatic de novo lipogenesis, including SREBP-1c, and fatty acid uptake and transport nih.gov. Studies indicate that PPARγ agonists can inhibit SREBP-1c promoter activity induced by Liver X Receptor (LXR) oup.com. This inhibition is mediated through the two LXR response elements (LXREs) within the SREBP-1c promoter region, and PPARs can reduce the binding of LXR/RXR to LXRE oup.com.

Anti-inflammatory and Immunomodulatory Effects

Beyond its metabolic actions, this compound exhibits notable anti-inflammatory and immunomodulatory effects, regulating various immune cells and cytokines tandfonline.commdpi.com. It has been recognized as a potential therapeutic candidate for autoimmune disorders, influencing diseases like systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis tandfonline.comnih.gov.

Reduction of Tumor Necrosis Factor Alpha (TNFα)

This compound significantly reduces the production and expression of pro-inflammatory cytokines, including Tumor Necrosis Factor Alpha (TNFα) tandfonline.comahajournals.orgoup.comresearchgate.netnih.gov. TNFα is a cytokine implicated in inflammation and insulin resistance nih.govtandfonline.comdiabetesjournals.org. This compound has been observed to suppress TNFα production in ischemic retinas of wild-type mice, and it can ameliorate TNFα-induced insulin resistance by restoring insulin-stimulated 2-deoxyglucose uptake, tyrosine phosphorylation, and protein levels of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) ahajournals.orgdiabetesjournals.orgnih.gov. This effect on insulin signaling appears to be independent of PPARγ's adipogenic activity diabetesjournals.orgnih.gov. Furthermore, this compound can directly inhibit TNFα expression and secretion from adipocytes nih.gov.

Squelching of Nuclear Co-factors for Nuclear Factor Kappa B (NF-κB)

This compound, through its action on PPARγ, can inhibit the activity of Nuclear Factor Kappa B (NF-κB), a master regulator of inflammatory responses mdpi.comoup.come-century.usnih.govlongdom.orgmdpi.com. One of the proposed mechanisms involves the "squelching" of nuclear co-factors e-century.usnih.govmdpi.com. PPARγ can scavenge transcriptional co-factors, such as steroid receptor co-activator-1 (SRC-1) and cAMP response element-binding protein (CREB) binding protein (CBP/p300) e-century.us. By binding to PPARγ, these co-factors become unavailable for initiating gene expression, thereby downregulating NF-κB-mediated gene expression e-century.us. Additionally, PPARγ can directly interfere with NF-κB's transcription-activating capacity or indirectly regulate proteins that suppress NF-κB activation, such as by inducing IκBα, the main endogenous inhibitor of NF-κB nih.govlongdom.orgmdpi.com.

Modulation of C-reactive protein (CRP) and Adiponectin Levels

This compound has been shown to modulate the levels of C-reactive protein (CRP) and adiponectin, which are important markers of inflammation and insulin sensitivity, respectively ahajournals.orgoup.comdiabetesjournals.orgnih.govscispace.comfrontiersin.org. This compound treatment leads to a significant decrease in circulating CRP concentrations and a significant increase in plasma adiponectin levels diabetesjournals.orgnih.govscispace.com. This increase in adiponectin contributes to the anti-inflammatory and insulin-sensitizing effects of this compound ahajournals.orgoup.com. Adiponectin, an anti-inflammatory adipokine, is often lower in obese individuals with dysregulated immune responses frontiersin.org.

Table 2: Modulation of Inflammatory Markers by this compound (4-week treatment in Type 2 Diabetic Patients)

Mitochondrial Metabolism and Biogenesis

Furthermore, this compound stimulates the expression of genes involved in the fatty acid oxidation pathway, such as carnitine palmitoyltransferase-1 (CPT1), malonyl-CoA decarboxylase, and medium-chain acyl-CoA dehydrogenase diabetesjournals.orgnih.gov. The expression of PPAR-alpha (PPARα), a transcriptional regulator of genes encoding mitochondrial enzymes involved in fatty acid oxidation, is also higher after this compound treatment diabetesjournals.orgnih.gov. In skeletal muscle, this compound therapy can restore insulin sensitivity, partly by coordinating the upregulation of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) and ribosomal protein biosynthesis plos.orgnih.gov. This effect may involve an increase in adiponectin, a direct effect on muscle PPARγ, and/or improved insulin action on mitochondrial biogenesis plos.org. This compound's ability to enhance mitochondrial biogenesis and oxidative phosphorylation may also be mediated via PrPC expression and is associated with improved ATP production researchgate.net.

Table 3: Gene Expression Changes Related to Mitochondrial Function with this compound Treatment

Mitochondrial Metabolism and Biogenesis

Activation of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α)

This compound, as a PPARγ agonist, has been consistently shown to upregulate the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) diabetesjournals.orgnih.govresearchgate.netmdpi.complos.orgscielo.br. This effect has been observed in various contexts, including human subcutaneous adipose tissue, Down Syndrome fetal fibroblasts, skeletal muscle of women with Polycystic Ovary Syndrome (PCOS), and lung tissues diabetesjournals.orgnih.govplos.orgscielo.br.

The activation and increased expression of PGC-1α by this compound drive several crucial downstream cellular processes:

Mitochondrial Biogenesis and Function: PGC-1α is a master regulator of mitochondrial biogenesis, leading to an increased mitochondrial copy number, enhanced mitochondrial DNA content, and improved mitochondrial respiratory capacity diabetesjournals.orgnih.govmdpi.complos.org. Studies have shown that this compound increases factors involved in mitochondrial biogenesis, including mitochondrial transcription factor A (mtTFA) diabetesjournals.org. It also upregulates the expression of genes required for fatty acid oxidation, such as PPAR-α, medium-chain acyl-CoA dehydrogenase (MCAD), carnitine palmitoyltransferase I (CPT-1), and malonyl-CoA decarboxylase (MLYCD) diabetesjournals.org. Furthermore, this compound can restore the mitochondrial network by influencing fission-fusion machinery, evidenced by the upregulation of optic atrophy 1 (OPA1) and mitofusin 1 (MFN1), and downregulation of dynamin-related protein 1 (DRP1) nih.gov.

Transcriptional Control: The upregulation of PGC-1α by this compound can be mediated, in part, by increased phosphorylation of AMPK nih.govresearchgate.net. PGC-1α also coactivates other key transcription factors, such as Nuclear Respiratory Factor 1 (NRF1) and Estrogen-related receptor (ERR)-alpha, which play vital roles in mediating mitochondrial biogenesis and oxidative metabolism mdpi.com.

Table 1: Impact of this compound on PGC-1α and Related Mitochondrial Markers

Expression of Superoxide Dismutases (SOD2)

This compound has been demonstrated to influence the expression of Superoxide Dismutases (SODs), particularly SOD2, a crucial mitochondrial antioxidant enzyme. This compound treatment leads to an upregulation of SOD2 mRNA and protein levels, and in some cases, also SOD1 and SOD3 jpp.krakow.plresearchgate.netnih.govresearcherslinks.com.

The mechanism behind this upregulation involves its interaction with PPARγ and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This compound, through PPARγ-dependent activation and subsequently through PPARγ-dependent activation of Nrf2, can enhance the expression of SOD1, SOD2, and SOD3 jpp.krakow.plresearchgate.netresearcherslinks.com. SOD2 (Manganese Superoxide Dismutase, Mn-SOD), primarily localized in the mitochondrial matrix and inner membrane, plays a critical role in cellular antioxidant defense by converting the superoxide anion radical (•O2-) into hydrogen peroxide (H2O2), thereby preventing oxidative damage nih.govmdpi.com. Research findings indicate that this compound's ability to upregulate these antioxidant defense mechanisms contributes to the attenuation of oxidative DNA damage, as observed in models of high-fat diet-induced hepatic oxidative stress nih.gov. This suggests a protective role of this compound against oxidative stress by enhancing the enzymatic antioxidant defense system.

Table 2: Influence of this compound on Superoxide Dismutase (SOD) Expression

Uncoupling Protein 1 (UCP-1) Expression in Adipose Tissue

This compound significantly impacts the expression of Uncoupling Protein 1 (UCP-1) in various adipose tissue depots. Studies have consistently shown that this compound increases UCP-1 expression in human subcutaneous adipose tissue, white adipose tissue (WAT) in mouse models (e.g., db/db mice), and brown adipose tissue (BAT) diabetesjournals.orgnih.govjci.orgnih.govresearchgate.netphysiology.org.

UCP-1 is a key marker of brown adipose tissue and beige adipocytes, playing a crucial role in non-shivering thermogenesis by uncoupling oxidative phosphorylation from ATP synthesis, leading to heat production diabetesjournals.orgnih.govjci.orgnih.govresearchgate.netphysiology.orgresearchgate.net. The induction of UCP-1 by this compound contributes to an enhanced thermogenic capacity physiology.orgresearchgate.net. This "browning" effect on white adipose tissue, where WAT depots acquire characteristics of BAT, is a notable finding, observed in both in vivo and in vitro studies diabetesjournals.orgjci.orgresearchgate.net. The increase in UCP-1 expression is associated with improved glucose and lipid homeostasis. jci.org

Impact on Islet Beta-Cell Health and Maturity Markers

This compound has a demonstrated impact on the health and maturity markers of pancreatic islet beta-cells, contributing to improved beta-cell function and survival.

Improved Function and Survival: In conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation, this compound has been shown to improve glucose-stimulated insulin secretion in pancreatic beta-cells e-enm.org. It also represses apoptosis, as evidenced by decreased caspase-3 cleavage e-enm.org.

Reduced Stress and Inflammation: this compound reverses palmitate-induced expression of inflammatory cytokines, such as tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), and IL-1β e-enm.org. Furthermore, it attenuates ER stress, reducing markers like glucose-regulated protein 78 (GRP78), cleaved-activating transcription factor 6 (ATF6), and C/EBP homologous protein (CHOP) e-enm.org. This protective effect is believed to be mediated, in part, by blocking the NFκB pathway e-enm.orgjcrpe.org.

Maturity Markers: Studies in db/db mice have shown that this compound treatment leads to greater expression of insulin and the transcription factor Nkx6.1 in pancreatic beta-cells, with a corresponding reduction in the abundance of the de-differentiation marker Aldh1a3 nih.govnih.govresearchgate.net. Nkx6.1 is a key marker of mature beta-cells, indicating that this compound helps restore and maintain beta-cell identity nih.gov. Additionally, this compound upregulates glucose transporter 2 (Glut2) expression in beta-cells, which is crucial for glucose sensing e-enm.org.

Preservation of Beta-Cell Mass: In animal models, long-term treatment with this compound has been linked to the preservation of beta-cell mass, primarily through the reduction of oxidative stress e-dmj.org. Clinical studies, such as the Actos Now for Prevention of Diabetes (ACT NOW) study, have shown that this compound can significantly improve insulin sensitivity and beta-cell function, contributing to a decreased rate of conversion from impaired glucose tolerance to type 2 diabetes e-dmj.org. Meta-analyses have further indicated that this compound can elevate the absolute value of homeostasis model assessment of β-cells (HOMA-β) plos.org.

Table 3: Effects of this compound on Islet Beta-Cell Health and Maturity