Non-alcoholic Fatty Liver Disease: A Review of Anti-diabetic Pharmacologic Therapies

Snyder, Heather; Sakaan, Sami; March, Katherine; Siddique, Osama; Cholankeril, Rosann; Cummings, Carolyn; Gadiparthi, Chiranjeevi; Ahmed, Aijaz; Cholankeril, George

doi:10.14218/jcth.2017.00050

Cited by 30 publications

(25 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study, we demonstrated that anagliptin treatment effectively prevents the development of inflammation, fibrosis, and tumors in the liver of MC4R-KO mice fed WD. Although growing evidence points to the therapeutic implications of certain types of anti-diabetic agents in NASH 23 , it is technically difficult to distinguish their effects on NASH from their effects on diabetes. For instance, it has been reported that DPP-4 inhibitors ameliorate lipid accumulation and insulin resistance in the liver, along with systemic glucose intolerance 6 .…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase-4 inhibition prevents nonalcoholic steatohepatitis–associated liver fibrosis and tumor development in mice independently of its anti-diabetic effects

Kawakubo

Tanaka

Ochi

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Nonalcoholic steatohepatitis (NASH) is a hepatic phenotype of the metabolic syndrome, and increases the risk of cirrhosis and hepatocellular carcinoma (HCC). Although increasing evidence points to the therapeutic implications of certain types of anti-diabetic agents in NASH, it remains to be elucidated whether their effects on NASH are independent of their effects on diabetes. Genetically obese melanocortin 4 receptor-deficient (MC4R-KO) mice fed Western diet are a murine model that sequentially develops hepatic steatosis, NASH, and HCC in the presence of obesity and insulin resistance. In this study, we investigated the effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor anagliptin on NASH and HCC development in MC4R-KO mice. Anagliptin treatment effectively prevented inflammation, fibrosis, and carcinogenesis in the liver of MC4R-KO mice. Interestingly, anagliptin only marginally affected body weight, systemic glucose and lipid metabolism, and hepatic steatosis. Histological data and gene expression analysis suggest that anagliptin treatment targets macrophage activation in the liver during the progression from simple steatosis to NASH. As a molecular mechanism underlying anagliptin action, we showed that glucagon-like peptide-1 suppressed proinflammatory and profibrotic phenotypes of macrophages in vitro. This study highlights the glucose metabolism-independent effects of anagliptin on NASH and HCC development.

show abstract

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase-4 inhibition prevents nonalcoholic steatohepatitis–associated liver fibrosis and tumor development in mice independently of its anti-diabetic effects

Kawakubo

Tanaka

Ochi

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Several epidemiological studies have revealed that weight gain greatly increases the risk and burden of hepatic steatosis and NAFLD with or without T2DM [3, 21–23]. It was reported recently that antidiabetics might become an attractive therapeutic option for treating patients with T2DM and NAFLD given their common pathophysiological features [24, 25].…”

Section: Discussionmentioning

confidence: 99%

Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway

Zhang

et al. 2019

International Journal of Endocrinology

View full text Add to dashboard Cite

A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway.

show abstract

“…It was supported by the rapid decline of insulin dosage from 7 day to 9 day. In maintenance therapy after SIIT, GLP-1 receptor agonist dulaglutide, metformin, and SGLT2 inhibitor empagliflozin are agents for treatment of fatty liver [48][49][50][51][52] . Voglibose and mitiglinide might contribute to the relief of NASH by subsiding post prandial hyperglycaemia.…”

Section: Discussionmentioning

confidence: 99%

Practical application of short-term intensive insulin therapy based on the concept of “treat to target” to reduce hypoglycaemia in routine clinical site

Nakashima

Okamura

Sanefuji

et al. 2020

Sci Rep

View full text Add to dashboard Cite

the aim is to devise a new short-term intensive insulin therapy (n-Siit) based on the concept of "treat to target" to avoid hypoglycaemia and was applied it to various diabetic state. We determined dosage of 1 basal and 3 bolus "treat" insulin based on "target" blood glucose level and changed each insulin dose by small units (2 units) every day for 2 weeks. We evaluated the effects of N-SIIT in 74 subjects with type 2 diabetes (male 45, female 29, 64.9 ± 16.6 years old, HbA1c 10.4 ± 2.6%). Glargine U300 ("treat") and morning blood glucose level ("target") was significantly correlated with increasing insulin dose and decreasing blood glucose level in day 1-7, indicating that insulin amount was determined by target blood glucose level and lowered next target blood glucose level. Remission rates were 67.3% (Hypoglycaemia rate 5.6 %) in N-SIIT and 47.3% (Hypoglycaemia rate 38.1%) in conventional SIIT. Required amount of insulin would be automatically determined, depending on each patient pathophysiology and life style. This method is pretty simple, flexible and cheap, and provides information about the dynamic pathophysiological alteration of insulin resistance and glucotoxicity from the profile of blood glucose levels and insulin shot.Type 2 diabetes mellitus (T2DM) is a progressive disease which gradually reduces pancreatic beta-cell function such as insulin secretory capacity and increases insulin resistance in various insulin target tissues 1,2 . Recently, short-term intensive insulin therapy (SIIT) is recommended in the treatment of newly diagnosed T2DM to eliminate glucotoxicity, to reduce beta-cell overload (beta-cell rest effect), to support residual beta-cells and to enhance insulin sensitivity 3-18 .In addition, pancreatic alpha-cell dysfunction may contribute to the metabolic dysfunction found in diabetic state, because post-prandial paradoxical hyperglucagonaemia leads to the elevation of blood glucose levels 19,20 . SIIT may also improve alpha-cell physiology 21-23 . Indeed, it is possible that stepwise addition of insulin leads to the reduction of hyperglucagonaemia.The evidence of this treatment has been presented to prove benefits in the treatment of T2DM. However, in most SIIT studies, after SIIT they did not use any anti-diabetic agents and evaluated the duration of glycaemic remission [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] . As the results, glycaemic remission was temporary, especially when beta-cell function was markedly deteriorated after SIIT. Retnakaran et al. regarded SIIT as an induction therapy and sequential treatment with anti-diabetic agents as a maintenance therapy 24 . Several kinds of anti-diabetic agents such as metformin or GLP-1 receptor activator had been used for a maintenance therapy, but sometimes re-induction of insulin therapy was necessary [24][25][26][27] . We used conventional SIIT for the elimination of glucotoxicity in clinical practice and thought that SIIT was useful not only in newly diagnosed T2DM but also under many kinds of diabetes conditions to ...

show abstract

Non-alcoholic Fatty Liver Disease: A Review of Anti-diabetic Pharmacologic Therapies

Cited by 30 publications

References 70 publications

Dipeptidyl peptidase-4 inhibition prevents nonalcoholic steatohepatitis–associated liver fibrosis and tumor development in mice independently of its anti-diabetic effects

Dipeptidyl peptidase-4 inhibition prevents nonalcoholic steatohepatitis–associated liver fibrosis and tumor development in mice independently of its anti-diabetic effects

Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway

Practical application of short-term intensive insulin therapy based on the concept of “treat to target” to reduce hypoglycaemia in routine clinical site

Contact Info

Product

Resources

About