Intranasal insulin improves the structure–function of the brain mitochondrial ATP–sensitive Ca2+ activated potassium channel and respiratory chain activities under diabetic conditions

Torabi, Nihad; Noursadeghi, Elham; Shayanfar, Farzad; Nazari, Maryam; Fahanik-Babaei, Javad; Saghiri, Reza; Khodagholi, Fariba; Eliassi, Afsaneh

doi:10.1016/j.bbadis.2021.166075

Cited by 15 publications

(13 citation statements)

References 87 publications

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“…To quantify the bands, densitometry of protein bands was performed using image J software. As positive controls, calnexin (# SC-46669, Santa Cruz), an ER marker, and β-actin (# ab8227, Abcam) antibodies were used 108 .…”

Section: Methodsmentioning

confidence: 99%

Endoplasmic reticulum stress inhibition ameliorated WFS1 expression alterations and reduced pancreatic islets’ insulin secretion induced by high-fat diet in rats

Binayi

Fahanik-Babaei

Salimi

et al. 2023

Sci Rep

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Endoplasmic reticulum (ER) stress is involved in the development of glucose homeostasis impairment. When ER stress occurs, the unfolded protein response (UPR) is activated to cope with it. One of the UPR components is WFS1 (Wolfram syndrome 1), which plays important roles in ER homeostasis and pancreatic islets glucose-stimulated insulin secretion (GSIS). Accordingly and considering that feeding high-fat food has a major contribution in metabolic disorders, this study aimed to investigate the possible involvement of pancreatic ER stress in glucose metabolism impairment induced by feeding high-fat diet (HFD) in male rats. After weaning, the rats were divided into six groups, and fed on normal diet and HFD for 20 weeks, then 4-phenyl butyric acid (4-PBA, an ER stress inhibitor) was administered. Subsequently, in all groups, after performing glucose tolerance test, the animals were dissected and their pancreases were removed to extract ER, islets isolation and assessment of GSIS. Moreover, the pancreatic ER stress [binding of immunoglobulin protein (BIP) and enhancer-binding protein homologous protein (CHOP)] and oxidative stress [malondialdehyde (MDA), glutathione (GSH) and catalase] biomarkers as well as WFS1 expression level were evaluated. HFD decreased pancreatic WFS1 protein and GSH levels, and enhanced pancreatic catalase activity, MDA content, BIP and CHOP protein and mRNA levels as well as Wfs1 mRNA amount. Accordingly, it increased BIP, CHOP and WFS1 protein levels in the extracted ER of pancreas. In addition, the HFD caused glucose intolerance, and decreased the islets’ GSIS and insulin content. However, 4-PBA administration restored the alterations. It seems that, HFD consumption through inducing pancreatic ER stress, altered WFS1 expression levels, reduced the islets’ GSIS and insulin content and finally impaired glucose homeostasis.

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Section: Methodsmentioning

confidence: 99%

Endoplasmic reticulum stress inhibition ameliorated WFS1 expression alterations and reduced pancreatic islets’ insulin secretion induced by high-fat diet in rats

Binayi

Fahanik-Babaei

Salimi

et al. 2023

Sci Rep

Self Cite

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“…The ability of insulin to normalize mitochondrial function in the brain, impaired in DM, can make a significant contribution to the neuroprotective effect of INI in diabetic pathology [ 312 , 313 ]. Treatment of male rats with streptozotocin DM with a relatively high dose of INI (10 IU/rat) for 11 days led to a significant restoration of complex I and IV of the mitochondrial respiratory chain in the brain and a decrease in the production of reactive oxygen species, and also improved the functional activity of mitochondrial ATP-sensitive large-conductance Ca 2+ -activated potassium (mitoBKCa) channels and increased expression of their β-subunit [ 313 ]. Our data on INI-induced normalization of the expression of genes involved in mitochondrial biogenesis and apoptosis in the hypothalamus of rats with T1DM support the normalizing effect of INI on mitochondrial function in DM [ 301 ].…”

Section: Intranasal Insulin and Diabetes Mellitusmentioning

confidence: 99%

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

Zorina

Derkach

2023

IJMS

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A decrease in the activity of the insulin signaling system of the brain, due to both central insulin resistance and insulin deficiency, leads to neurodegeneration and impaired regulation of appetite, metabolism, endocrine functions. This is due to the neuroprotective properties of brain insulin and its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine, and other systems. One of the approaches to restore the activity of the insulin system of the brain is the use of intranasally administered insulin (INI). Currently, INI is being considered as a promising drug to treat Alzheimer’s disease and mild cognitive impairment. The clinical application of INI is being developed for the treatment of other neurodegenerative diseases and improve cognitive abilities in stress, overwork, and depression. At the same time, much attention has recently been paid to the prospects of using INI for the treatment of cerebral ischemia, traumatic brain injuries, and postoperative delirium (after anesthesia), as well as diabetes mellitus and its complications, including dysfunctions in the gonadal and thyroid axes. This review is devoted to the prospects and current trends in the use of INI for the treatment of these diseases, which, although differing in etiology and pathogenesis, are characterized by impaired insulin signaling in the brain.

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“…Wingrove et al (2019) reported that inhaled insulin administration uses the nose-brain pathway and delivers the drug directly to the brain tissue while limiting systemic exposure [108]. Insulin administered in this way appears to improve the potential of the brain's mitochondrial membrane and stimulates the activity of the brain's mitochondrial complexes in a streptozotocin-induced model of early type 2 diabetes [109]. Injections of lipopolysaccharide (LPS) into the brain ventricles of rats caused inflammation of the nervous system.…”

Section: The Importance Of Vitamins and Hormonesmentioning

confidence: 99%

Importance of Bioactive Substances in Sheep’s Milk in Human Health

Flis

Molik

2021

IJMS

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Sheep’s milk is an important source of bioactive substances that have health-promoting functions for the body. The valuable composition of sheep’s milk is due to the high content of fatty acids, immunoglobulins, proteins, hormones, vitamins and minerals. Many biopeptides found in milk have antibacterial, antiviral and anti-inflammatory properties. The bioactive substances of sheep’s milk also show anticancer properties. Sheep’s milk, thanks to its content of CLA and orotic acid, prevents the occurrence of type 2 diabetes, Alzheimer’s disease and cancer. Sheep’s milk, as a product rich in bioactive substances, can be used as a medical aid to support the body in the fight against neurological and cancer diseases.

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Intranasal insulin improves the structure–function of the brain mitochondrial ATP–sensitive Ca2+ activated potassium channel and respiratory chain activities under diabetic conditions

Cited by 15 publications

References 87 publications

Endoplasmic reticulum stress inhibition ameliorated WFS1 expression alterations and reduced pancreatic islets’ insulin secretion induced by high-fat diet in rats

Endoplasmic reticulum stress inhibition ameliorated WFS1 expression alterations and reduced pancreatic islets’ insulin secretion induced by high-fat diet in rats

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

Importance of Bioactive Substances in Sheep’s Milk in Human Health

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