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Article ; Online: GLP-1 receptor agonists in the treatment of diabetic non-alcoholic steatohepatitis patients.

Adeghate, Ernest A

2024 Volume 25, Issue 3, Page(s) 223–232

Abstract: Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease affecting almost 30% of the world population. Approximately 25% of people with NAFLD develop nonalcoholic steatohepatitis (NASH), the fulminant version of the ... ...

Abstract	Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease affecting almost 30% of the world population. Approximately 25% of people with NAFLD develop nonalcoholic steatohepatitis (NASH), the fulminant version of the disease. Diabetes mellitus is present in 22.5% of people with NAFLD and 44.60% of individuals with NASH. This review was undertaken to examine the current contribution of glucagon-like peptide 1 (GLP-1) receptor agonists to the pharmacotherapy of diabetic nonalcoholic steatohepatitis. Areas covered: The author analyzed the current status of GLP-1 receptor agonists for pharmacotherapy of diabetic NASH. Research data and literature reports were taken from the database and or websites of Diabetes UK, American Diabetes Association, ClinicalTrials.gov, PubMed, and Scopus. The keywords utilized included type 2 diabetes, GLP-1, NASH, NAFLD, and clinical trials. Expert opinion: Since diabetic NASH is associated with obesity, diabetes mellitus, oxidative stress and inflammation, drugs capable of mitigating all of these conditions simultaneously, are most ideal for the treatment of diabetic NASH. These drugs include (in order of relevance), GLP-1 receptor agonists, GLP-1 and GIP dual receptor agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and pioglitazone. The future, FDA-approved drug for diabetic NASH treatment will likely be GLP-1 agonist, which could be used as monotherapy or in combination with other drugs.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/complications ; Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use ; Hypoglycemic Agents/therapeutic use ; Non-alcoholic Fatty Liver Disease/drug therapy
Chemical Substances	Glucagon-Like Peptide-1 Receptor Agonists ; Hypoglycemic Agents
Language	English
Publishing date	2024-03-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2024.2328796
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Article ; Online: An Update on the Molecular and Cellular Basis of Pharmacotherapy in Type 2 Diabetes Mellitus.

Mahgoub, Mohamed Omer / Ali, Ifrah Ismail / Adeghate, Jennifer O / Tekes, Kornélia / Kalász, Huba / Adeghate, Ernest A

International journal of molecular sciences

2023 Volume 24, Issue 11

Abstract: Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number is steadily increasing. The worldwide number of people suffering from DM is ... ...

Abstract	Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number is steadily increasing. The worldwide number of people suffering from DM is projected to reach 783 million in 2045. In 2021 alone, more than USD 966 billion was spent on the management of DM. Reduced physical activity due to urbanization is believed to be the major cause of the increase in the incidence of the disease, as it is associated with higher rates of obesity. Diabetes poses a risk for chronic complications such as nephropathy, angiopathy, neuropathy and retinopathy. Hence, the successful management of blood glucose is the cornerstone of DM therapy. The effective management of the hyperglycemia associated with type 2 diabetes includes physical exercise, diet and therapeutic interventions (insulin, biguanides, second generation sulfonylureas, glucagon-like peptide 1 agonists, dipeptidyl-peptidase 4 inhibitors, thiazolidinediones, amylin mimetics, meglitinides, α-glucosidase inhibitors, sodium-glucose cotransporter-2 inhibitors and bile acid sequestrants). The optimal and timely treatment of DM improves the quality of life and reduces the severe burden of the disease for patients. Genetic testing, examining the roles of different genes involved in the pathogenesis of DM, may also help to achieve optimal DM management in the future by reducing the incidence of DM and by enhancing the use of individualized treatment regimens.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Hypoglycemic Agents/therapeutic use ; Hypoglycemic Agents/pharmacology ; Quality of Life ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
Chemical Substances	Hypoglycemic Agents ; Sodium-Glucose Transporter 2 Inhibitors ; Dipeptidyl-Peptidase IV Inhibitors
Language	English
Publishing date	2023-05-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24119328
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Article ; Online: Mechanisms of COVID-19-induced heart failure: a short review.

Adeghate, Ernest A / Eid, Nabil / Singh, Jaipaul

Heart failure reviews

2020 Volume 26, Issue 2, Page(s) 363–369

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected more than 42.5 million people globally resulting in the death of over 1.15 million subjects. It has inflicted severe public ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected more than 42.5 million people globally resulting in the death of over 1.15 million subjects. It has inflicted severe public health and economic hardships across the world. In addition to acute respiratory distress syndrome, respiratory failure, sepsis, and acute kidney injury, COVID-19 also causes heart failure (HF). COVID-19-induced HF is manifested via different mechanisms, including, but not limited to, (1) virus-induced infiltration of inflammatory cells, which could impair the function of the heart; (2) pro-inflammatory cytokines (monocyte chemoattractant protein-1, interleukin-1β; interleukin-6; tumor necrosis factor-α) that could cause necrosis and death of the myocardium; (3) endothelial injury coupled with micro-thrombosis which could damage the endocardium; and (4) acute respiratory distress syndrome and respiratory failure that could lead to heart failure due to severe hypoxia. It is concluded that the etiology of COVID-19-induced HF is multifactorial and mitigation of the development of HF in patients with COVID-19 will require different approaches such as social distancing, drug therapy, and the urgent development of a vaccine to eradicate the disease.
MeSH term(s)	COVID-19/complications ; Heart Failure/etiology ; Humans
Keywords	covid19
Language	English
Publishing date	2020-11-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1336499-6
ISSN	1573-7322 ; 1382-4147
ISSN (online)	1573-7322
ISSN	1382-4147
DOI	10.1007/s10741-020-10037-x
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Article ; Online: High-Density Lipoprotein Is Located Alongside Insulin in the Islets of Langerhans of Normal and Rodent Models of Diabetes.

Mohsin, Sahar / Elabadlah, Haba / Alotaiba, Mariam K / AlAmry, Suhail / Almehairbi, Shamma J / Harara, Maha M K / Almuhsin, Aisha M H / Tariq, Saeed / Howarth, Frank Christopher / Adeghate, Ernest A

Nutrients

2024 Volume 16, Issue 2

Abstract: Recent studies have implicated pre-beta and beta lipoproteins (VLDL and LDL) in the etiopathogenesis of complications of diabetes mellitus (DM). In contrast, alpha lipoprotein (HDL) is protective of the beta cells of the pancreas. This study examined the ...

Abstract	Recent studies have implicated pre-beta and beta lipoproteins (VLDL and LDL) in the etiopathogenesis of complications of diabetes mellitus (DM). In contrast, alpha lipoprotein (HDL) is protective of the beta cells of the pancreas. This study examined the distribution of HDL in the islets of Langerhans of murine models of type 1 diabetic rats (streptozotocin (STZ)-induced DM in Wistar rats) and type 2 models of DM rats (Goto-Kakizaki (GK), non-diabetic Zucker lean (ZL), and Zucker diabetic and fatty (ZDF)). The extent by which HDL co-localizes with insulin or glucagon in the islets of the pancreas was also investigated. Pancreatic tissues of Wistar non-diabetic, diabetic Wistar, GK, ZL, and ZDF rats were processed for immunohistochemistry. Pancreatic samples of GK rats fed with either a low-fat or a high-fat diet were prepared for transmission immune-electron microscopy (TIEM) to establish the cytoplasmic localization of HDL in islet cells. HDL was detected in the core and periphery of pancreatic islets of Wistar non-diabetic and diabetic, GK, ZL, and ZDF rats. The average total of islet cells immune positive for HDL was markedly (<0.05) reduced in GK and ZDF rats in comparison to Wistar controls. The number of islet cells containing HDL was also remarkably (
MeSH term(s)	Rats ; Mice ; Animals ; Insulin/metabolism ; Glucagon/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Rodentia ; Lipoproteins, HDL/metabolism ; Rats, Wistar ; Rats, Zucker ; Islets of Langerhans/metabolism ; Pancreatic Hormones/metabolism ; Diabetes Mellitus, Type 2/metabolism
Chemical Substances	Insulin ; Glucagon (9007-92-5) ; Lipoproteins, HDL ; Pancreatic Hormones
Language	English
Publishing date	2024-01-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu16020313
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Article: Melatonin increases AKT and SOD gene and protein expressions in diabetic rats.

Lotfy, Mohamed / Khattab, Aalaa / Shata, Mohammed / Alhasbani, Ahmad / Khalaf, Abdallah / Alsaeedi, Saeed / Thaker, Mahdi / Said, Hazza / Tumi, Harun / Alzahmi, Hassan / Alblooshi, Omar / Hamdan, Mohamad / Hussein, Amjad / Kundu, Biduth / Adeghate, Ernest A

Heliyon

2024 Volume 10, Issue 7, Page(s) e28639

Abstract: Diabetes mellitus (DM) is a chronic metabolic disease marked by hyperglycemia due to insulin deficiency or insulin resistance leading to many chronic complications. It is thus important to manage diabetes effectively in order to prevent and or delay ... ...

Abstract	Diabetes mellitus (DM) is a chronic metabolic disease marked by hyperglycemia due to insulin deficiency or insulin resistance leading to many chronic complications. It is thus important to manage diabetes effectively in order to prevent and or delay these complications. Melatonin is produced by the pineal gland and regulates the wake-sleep circadian rhythm. Existing evidence suggests that melatonin may be effective in the management of DM. However, the evidence on the mechanism of the beneficial effect melatonin as a treatment for DM is limited. In this study, we investigated the effect of melatonin treatment on blood glucose, insulin (INS), AKT and superoxide dismutase (SOD) gene levels in diabetic rats. Non-diabetic and diabetic rats were treated orally for 4 weeks with either 25 mg or 50 mg/kg body weight of melatonin. At the end of the study, pancreatic and liver tissues morphology, glucose homeostasis, serum insulin and SOD levels, hepatic gene and protein expression of SOD as protecting antioxidant enzyme and AKT as central element involved in PI3K/AKT insulin signaling pathway were estimated. Melatonin treated diabetic rats showed reduced hyperglycemia, and increased serum insulin and SOD levels. In addition, melatonin induced an increased gene and protein expression of SOD and AKT. In conclusion, melatonin may play a role in treating diabetic rats via stimulation of insulin secretion, insulin signaling and reduction in oxidative stress.
Language	English
Publishing date	2024-03-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e28639
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Article ; Online: Mechanisms of COVID-19-induced heart failure

Adeghate, Ernest A. / Eid, Nabil / Singh, Jaipaul

a short review

2020

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected more than 23 million people globally resulting in the death of over 800,000 subjects. It has inflicted severe public health and ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected more than 23 million people globally resulting in the death of over 800,000 subjects. It has inflicted severe public health and economic hardships across the world. In addition to acute respiratory distress syndrome, respiratory failure, sepsis, and acute kidney injury, COVID-19 also causes heart failure (HF). COVID-19-induced HF is manifested via different mechanisms, including, but not limited to, (1) virus-induced infiltration of inflammatory cells, which could impair the function of the heart; (2) pro-inflammatory cytokines (monocyte chemoattractant protein-1, interleukin-1β; interleukin-6; tumor necrosis factor-α) that could cause necrosis and death of the myocardium; (3) endothelial injury coupled with micro-thrombosis which could damage the endocardium; and (4) acute respiratory distress syndrome and respiratory failure that could lead to heart failure due to severe hypoxia. It is concluded that the etiology of COVID-19-induced HF is multifactorial and mitigation of the development of HF in patients with COVID-19 will require different approaches such as social distancing, drug therapy, and the urgent development of a vaccine to eradicate the disease.
Keywords	Forensic science ; covid19
Subject code	610
Language	English
Publishing date	2020-10-22
Publisher	Springer
Publishing country	uk
Document type	Article ; Online
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Article ; Online: Exogenous Ghrelin Increases Plasma Insulin Level in Diabetic Rats.

Elabadlah, Haba / Hameed, Rasheed / D'Souza, Crystal / Mohsin, Sahar / Adeghate, Ernest A

Biomolecules

2020 Volume 10, Issue 4

Abstract: Ghrelin, a 28-amino acid peptide, is a strong growth hormone secretagogue and a regulator of food intake. In addition, ghrelin is thought to play a role in insulin secretion and in glucose homeostasis. A lot of contradictory data have been reported in ... ...

Abstract	Ghrelin, a 28-amino acid peptide, is a strong growth hormone secretagogue and a regulator of food intake. In addition, ghrelin is thought to play a role in insulin secretion and in glucose homeostasis. A lot of contradictory data have been reported in the literature regarding the co-localization of ghrelin with other hormones in the islet of Langerhans, its role in insulin secretion and attenuation of type 2 diabetes mellitus. In this study, we investigate the effect of chronic ghrelin treatment on glucose, body weight and insulin level in normal and streptozotocin-induced diabetic male Wistar rats. We have also examined the distribution pattern and co-localization of ghrelin with insulin in pancreatic islet cells using immunohistochemistry and immune-electron microscopy and the ability of ghrelin to stimulate insulin release from the CRL11065 beta cell line. Control, non-diabetic groups received intraperitoneal injection of normal saline, while treated groups received intraperitoneal injection of 5 µg/kg body weight of ghrelin (amino acid chain 24-51) on a daily basis for a duration of four weeks. Our results show that the administration of ghrelin increases the number of insulin-secreting beta cells and serum insulin level in both normal and diabetic rats. We also demonstrated that ghrelin co-localizes with insulin in pancreatic islet cells and that the pattern of ghrelin distribution is altered after the onset of diabetes. Moreover, ghrelin at a dose of 10-6M and 10-12M increased insulin release from the CRL11065 beta cell line. In summary, ghrelin co-localizes with insulin in the secretory granules of pancreatic beta cells and enhances insulin production.
MeSH term(s)	Animals ; Blood Glucose/metabolism ; Body Weight/drug effects ; Diabetes Mellitus, Experimental/blood ; Fasting/blood ; Ghrelin/pharmacology ; Glucose Tolerance Test ; Insulin/blood ; Insulin Secretion/drug effects ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Insulin-Secreting Cells/ultrastructure ; Male ; Rats, Wistar ; Signal Transduction/drug effects
Chemical Substances	Blood Glucose ; Ghrelin ; Insulin
Language	English
Publishing date	2020-04-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom10040633
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Article ; Online: Tackling type 2 diabetes-associated cardiovascular and renal comorbidities: a key challenge for drug development.

Adeghate, Ernest A / Kalász, Huba / Al Jaberi, Saeeda / Adeghate, Jennifer / Tekes, Kornelia

Expert opinion on investigational drugs

2020 Volume 30, Issue 2, Page(s) 85–93

MeSH term(s)	Animals ; Cardiovascular Diseases/prevention & control ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetic Nephropathies/prevention & control ; Drug Development ; Humans ; Hypoglycemic Agents/therapeutic use
Chemical Substances	Hypoglycemic Agents
Language	English
Publishing date	2020-12-28
Publishing country	England
Document type	Editorial
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1080/13543784.2021.1865914
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Article: Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats.

Adeghate, Ernest / D'Souza, Crystal M / Saeed, Zulqarnain / Al Jaberi, Saeeda / Tariq, Saeed / Kalász, Huba / Tekes, Kornélia / Adeghate, Ernest A

Biology

2021 Volume 10, Issue 7

Abstract: Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous ... ...

Abstract	Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1-17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (
Language	English
Publishing date	2021-07-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10070621
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Article ; Online: Lipocalin-2: Structure, function, distribution and role in metabolic disorders.

Jaberi, Saeeda Al / Cohen, Athena / D'Souza, Crystal / Abdulrazzaq, Yousef M / Ojha, Shreesh / Bastaki, Salim / Adeghate, Ernest A

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2021 Volume 142, Page(s) 112002

Abstract: Lipocalin-2 (LCN-2) is a novel, 198 amino acid adipocytokine also referred to as neutrophil gelatinase-associated lipocalin (NGAL). LCN-2 is a circulatory protein responsible for the transportation of small and hydrophobic molecules (steroid, free fatty ... ...

Abstract	Lipocalin-2 (LCN-2) is a novel, 198 amino acid adipocytokine also referred to as neutrophil gelatinase-associated lipocalin (NGAL). LCN-2 is a circulatory protein responsible for the transportation of small and hydrophobic molecules (steroid, free fatty acids, prostaglandins and hormones) to target organs after binding to megalin/glycoprotein and GP330 SLC22A17 or 24p3R LCN-2 receptors. LCN-2 has been used as a biomarker for acute and chronic renal injury. It is present in a large variety of cells including neutrophil, hepatocytes, lung, bone marrow, adipose tissue, macrophages, thymus, non-neoplastic breast duct, prostate, and renal cells. Different functions have been associated with LCN-2. These functions include antibacterial, anti-inflammatory, and protection against cell and tissue stress. Moreover, LCN-2 can increase the pool of matrix metalloproteinase 9 in human neutrophil granulocytes. Other reported functions of LCN-2 include its ability to destroy the extracellular matrix, which could enable cancer progression and spread of metastasis. Recent reports show that the tissue level of LCN-2 is increased in metabolic disorders such as obesity and type 2 diabetes, suggesting an association between LCN-2 and insulin sensitivity and glucose homeostasis. The precise role of LCN-2 in the modulation of insulin sensitivity, glucose and lipid metabolism is still unclear. This review explores the structure of LCN-2, tissue distribution, and its interaction with important metabolic pathways.
MeSH term(s)	Animals ; Diabetes Mellitus, Type 2/physiopathology ; Extracellular Matrix/metabolism ; Glucose/metabolism ; Humans ; Insulin Resistance ; Lipid Metabolism/physiology ; Lipocalin-2/chemistry ; Lipocalin-2/metabolism ; Metabolic Diseases/physiopathology ; Obesity/physiopathology
Chemical Substances	LCN2 protein, human ; Lipocalin-2 ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-08-27
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2021.112002
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