Hepatic function of glucagon-like peptide-1 and its based diabetes drugs.

Incretins are gut-produced peptide-hormones that potentiate insulin secretion, especially after food intake. The concept of incretin was formed more than 100 years ago, even before insulin was isolated and utilized in the treatment of subjects with type 1 diabetes. The first incretin, glucose-dependent insulinotropic polypeptide (GIP), was identified during later 1960's and early 1970's; while the second one, known as glucagon-like peptide-1 (GLP-1), was recognized during 1980's.

Improving the accuracy of the SRK/T formula in Chinese with implanting less than 10 D IOL calculated by the SRK/T formula: the SRK/T-Li formula.

Purpose: To explore the accuracy of the improved SRK/T-Li formula in eyes following implantation of intraocular lens (IOL) of less than 10 D as calculated by using the SRK/T formula in Chinese.

Methods: A total of 489 eyes from 489 patients with cataracts were included in this study. These patients were divided into a training set (271 patients) and a testing set (218 patients).

Fibroblast growth factor 21 and dietary interventions: what we know and what we need to know next.

Dietary interventions include the change of dietary styles, such as fasting and dietary or nutrient restrictions; or the addition of plant-derived compounds (such as polyphenols known as curcumin, resveratrol, or anthocyanin, or other nutraceuticals) into the diet. During the past a few decades, large number of studies have demonstrated therapeutic activities of these dietary interventions on metabolic and other diseases in human subjects or various animal models. Mechanisms underlying those versatile therapeutic activities, however, remain largely unclear.

Refractive outcomes of toric intra-ocular lens implantation in cases of high posterior corneal astigmatism.

Purpose: To evaluate whether the toric intra-ocular lens (IOL) power calculation based on total corneal astigmatism (TCA) in eyes with high posterior corneal astigmatism (PCA) could result in a systematic over-correction or under-correction after operation.

Methods: The present study included a mono-centric retrospective study design. The data were collected from 62 consecutive eyes during uncomplicated cataract surgery by a single surgeon with a measured PCA of 0.

Resveratrol intervention attenuates chylomicron secretion via repressing intestinal FXR-induced expression of scavenger receptor SR-B1.

Two common features of dietary polyphenols have hampered our mechanistic understanding of their beneficial effects for decades: targeting multiple organs and extremely low bioavailability. We show here that resveratrol intervention (REV-I) in high-fat diet (HFD)-challenged male mice inhibits chylomicron secretion, associated with reduced expression of jejunal but not hepatic scavenger receptor class B type 1 (SR-B1). Intestinal mucosa-specific SR-B1 mice on HFD-challenge exhibit improved lipid homeostasis but show virtually no further response to REV-I.

Short-term semaglutide treatment improves FGF21 responsiveness in primary hepatocytes isolated from high fat diet challenged mice.

Metabolic functions of GLP-1 and its analogues have been extensively investigated. In addition to acting as an incretin and reducing body weight, we and others have suggested the existence of GLP-1/fibroblast growth factor 21 (FGF21) axis in which liver mediates certain functions of GLP-1 receptor agonists. In a more recent study, we found with surprise that four-week treatment with liraglutide but not semaglutide stimulated hepatic FGF21 expression in HFD-challenged mice.

An evaluation of the accuracy of toric intraocular lens power calculation based on measured total corneal refractive power.

Purpose: To evaluate a method using measured values of total corneal refractive power (TCRP) for a manufacturer's online calculator by comparing it with the Barrett toric calculator (BTC) and Kane toric calculator (KTC) combined with simulated keratometry values (SimK).

Methods: This was a retrospective case series. Patient records were reviewed to identify the patients who had biometry with the IOL Master 700 and Pentacam recorded before toric IOL implantation and refractive follow-up data after implantation.

The anti-inflammatory feature of glucagon-like peptide-1 and its based diabetes drugs-Therapeutic potential exploration in lung injury.

Since 2005, GLP-1 receptor (GLP-1R) agonists (GLP-1RAs) have been developed as therapeutic agents for type 2 diabetes (T2D). GLP-1R is not only expressed in pancreatic islets but also other organs, especially the lung. However, controversy on extra-pancreatic GLP-1R expression still needs to be further resolved, utilizing different tools including the use of more reliable GLP-1R antibodies in immune-staining and co-immune-staining.

Hepatic hormone FGF21 and its analogues in clinical trials.

Fibroblast growth factor 21 (FGF21) is a fasting or stress inducible metabolic hormone produced mainly in the liver. It plays important roles in regulating both glucose and lipid homeostasis via interacting with a heterodimeric receptor complex comprising FGF receptor 1 (FGFR1) and β-klotho (KLB). For the past decade, great effort has been made on developing FGF21 derivatives or specific FGF21 receptor agonists into therapeutic agents for various metabolic disorders including type 2 diabetes (T2D), obesity, and more importantly, nonalcoholic fatty liver disease (NAFLD).

Comparison of Beneficial Metabolic Effects of Liraglutide and Semaglutide in Male C57BL/6J Mice.

Objectives: Semaglutide and liraglutide are glucagon-like peptide-1 (GLP-1)-based diabetes drugs. Semaglutide possesses a longer half-life. Utilizing relatively lower doses, we compared the beneficial metabolic effects of these 2 drugs in mice fed a high-fat diet (HFD), aiming to deepen our mechanistic understanding on their energy homeostatic functions.

Liraglutide stimulates the β-catenin signaling cascade in mouse epididymal fat tissue.

Although canonical Wnt signaling pathway activation was shown to negatively regulate adipogenesis, recent investigations suggest that Wnt pathway effectors TCF7L2 and β-catenin (β-cat) in adipose tissues are also involved in energy homeostasis during adulthood. In assessing the metabolic beneficial effect of GLP-1-based diabetes drugs in high-fat diet (HFD)-challenged mice, we observed that liraglutide treatment affected the expression of a battery of adipose tissue-specific genes, including those that encode adiponectin and leptin, mainly in epididymal white adipose tissue (eWAT). Fourteen-week HFD challenge repressed TCF7L2 and β-cat S675 phosphorylation in eWAT, while such repression was reversed by liraglutide treatment (150 µg/kg body weight daily) during weeks 10-14.

Estrogen-Wnt signaling cascade regulates expression of hepatic fibroblast growth factor 21.

We have generated the transgenic mouse line in which dominant negative TCF7L2 (TCF7L2DN) is specifically expressed in the liver during adulthood. Male but not female mice showed elevated hepatic and plasma triglyceride (TG) levels, indicating the existence of estrogen-β-cat/TCF signaling cascade that regulates hepatic lipid homeostasis. We show here that hepatic fibroblast growth factor 21 (FGF21) expression was reduced in male but not in female mice.

Epigenetic regulation of TXNIP-mediated oxidative stress and NLRP3 inflammasome activation contributes to SAHH inhibition-aggravated diabetic nephropathy.

S-adenosylhomocysteine (SAH) is hydrolyzed by SAH hydrolase (SAHH) to homocysteine and adenosine. Increased plasma SAH levels were associated with disturbed renal function in patients with diabetes. However, the role and mechanism of SAHH in diabetic nephropathy is still unknown.

Hepatic Fibroblast Growth Factor 21 Is Involved in Mediating Functions of Liraglutide in Mice With Dietary Challenge.

Background And Aims: Several studies have shown that expression of hepatic fibroblast growth factor 21 (FGF21) can be stimulated by glucagon-like peptide 1 (GLP-1)-based diabetes drugs. As GLP-1 receptor (GLP-1R) is unlikely to be expressed in hepatocytes, we aimed to compare such stimulation in mice and in mouse hepatocytes, determine the involvement of GLP-1R, and clarify whether FGF21 mediates certain functions of the GLP-1R agonist liraglutide.

Approach And Results: Liver FGF21 expression was assessed in mice receiving a daily liraglutide injection for 3 days or in mouse primary hepatocytes (MPHs) undergoing direct liraglutide treatment.

Friend or foe? ACE2 inhibitors and GLP-1R agonists in COVID-19 treatment.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a pandemic since WHO made the statement on March 11, 2020. The infection is causing a high mortality in old people, especially those with obesity, type 2 diabetes (T2D) or cardiovascular diseases (CVD). Extra cautions are needed in the treatment of those patients.

Current understanding and controversies on the clinical implications of fibroblast growth factor 21.

Metabolic functions of the hepatic hormone fibroblast growth factor 21 (FGF21) have been recognized for more than a decade in studying the responses of human subjects and rodent models to nutritional stresses such as fasting, high-fat diet or ketogenic diet consumption, and ethanol intake. Our interest in the beneficial metabolic effects of FGF21 has risen due to its potential ability to serve as a therapeutic agent for various metabolic disorders, including type 2 diabetes, obesity, and fatty liver diseases, as well as its potential to act as a diagnostic or prognostic biomarker for metabolic and other disorders. Here, we briefly review the FGF21 gene and protein structures, its expression pattern, and cellular signaling cascades that mediate FGF21 production and function.

Combined use of GABA and sitagliptin promotes human β-cell proliferation and reduces apoptosis.

γ-Aminobutyric acid (GABA) and glucagon-like peptide-1 receptor agonist (GLP-1RA) improve rodent β-cell survival and function. In human β-cells, GABA exerts stimulatory effects on proliferation and anti-apoptotic effects, whereas GLP-1RA drugs have only limited effects on proliferation. We previously demonstrated that GABA and sitagliptin (Sita), a dipeptidyl peptidase-4 inhibitor which increases endogenous GLP-1 levels, mediated a synergistic β-cell protective effect in mice islets.

Glucagon-like peptide-1 receptor mediates the beneficial effect of liraglutide in an acute lung injury mouse model involving the thioredoxin-interacting protein.

Repurposing clinically used drugs is among the important strategies in drug discovery. Glucagon-like peptide-1 (GLP-1) and its diabetes-based drugs, such as liraglutide, possess a spectrum of extra-pancreatic functions, while GLP-1 receptor (GLP-1R) is most abundantly expressed in the lung. Recent studies have suggested that GLP-1-based drugs exert beneficial effects in chronic, as well as acute, lung injury rodent models.

GABA requires GLP-1R to exert its pancreatic function during STZ challenge.

Gamma-aminobutyric acid (GABA) administration attenuates streptozotocin (STZ)-induced diabetes in rodent models with unclear underlying mechanisms. We found that GABA and Sitagliptin possess additive effect on pancreatic β-cells, which prompted us to ask the existence of common or unique targets of GLP-1 and GABA in pancreatic β-cells. Effect of GABA on expression of thioredoxin-interacting protein (TxNIP) was assessed in the INS-1 832/13 (INS-1) cell line, WT and GLP-1R-/- mouse islets.

Dietary Cyanidin-3-Glucoside Attenuates High-Fat-Diet-Induced Body-Weight Gain and Impairment of Glucose Tolerance in Mice via Effects on the Hepatic Hormone FGF21.

Background: Dietary polyphenols including anthocyanins target multiple organs.

Objective: We aimed to assess the involvement of glucagon-like peptide 1 (GLP-1), leptin, insulin and fibroblast growth factor 21 (FGF21) in mediating metabolic beneficial effects of purified anthocyanin cyanidin-3-glucoside (Cy3G).

Methods: Intestinal proglucagon gene (Gcg; encoding GLP-1) and liver Fgf21 expression were assessed in 6-wk-old male C57BL-6J mice fed a low-fat-diet (LFD; 10% of energy from fat), alone or with 1.