scholarly journals Oxytocin as a Metabolic Modulator

2021 ◽  
Author(s):  
Neeru Bhatt
Keyword(s):  
Diabetes Mellitus ◽  
Enzyme Activity ◽  
Developmental Trajectories ◽  
Sugar Metabolism ◽  
Peptide Hormone ◽  
Endocrine Disorders ◽  
Metabolic Hormones ◽  
Amino Acid Peptide ◽  
G Protein Coupled ◽  
Receptor Family

Oxytocin (9-amino acid peptide) hormone is a member of the G-protein coupled receptor family. It regulates a range of physiologic actions in mammals other than assisting parturition and lactation functions. Evidence indicates that oxytocin alters lipids, protein, and sugar metabolism through various ways including modulation of appetite and satiety, enzyme activity, cellular signals, secretion of metabolic hormones, and energy consumption. Alterations in these processes have the potential to shift developmental trajectories and influence disease processes. Oxytocin can be a potential avenue for the treatment of endocrine disorders such as obesity, diabetes mellitus, and associated disorders. The chapter will include a comprehensive study about oxytocin and its physiological and pathological functions, which makes it a potential target for drug therapy.

scholarly journals Crystal structure of the human oxytocin receptor

2020 ◽  
Vol 6 (29) ◽  
pp. eabb5419 ◽  
Author(s):  
Yann Waltenspühl ◽  
Jendrik Schöppe ◽  
Janosch Ehrenmann ◽  
Lutz Kummer ◽  
Andreas Plückthun
Keyword(s):  
Crystal Structure ◽  
Preterm Labor ◽  
Peptide Hormone ◽  
Oxytocin Receptor ◽  
Oral Drug ◽  
Allosteric Modulator ◽  
Agonist Binding ◽  
Positive Allosteric Modulator ◽  
G Protein Coupled ◽  
Receptor Family

The peptide hormone oxytocin modulates socioemotional behavior and sexual reproduction via the centrally expressed oxytocin receptor (OTR) across several species. Here, we report the crystal structure of human OTR in complex with retosiban, a nonpeptidic antagonist developed as an oral drug for the prevention of preterm labor. Our structure reveals insights into the detailed interactions between the G protein–coupled receptor (GPCR) and an OTR-selective antagonist. The observation of an extrahelical cholesterol molecule, binding in an unexpected location between helices IV and V, provides a structural rationale for its allosteric effect and critical influence on OTR function. Furthermore, our structure in combination with experimental data allows the identification of a conserved neurohypophyseal receptor-specific coordination site for Mg2+ that acts as potent, positive allosteric modulator for agonist binding. Together, these results further our molecular understanding of the oxytocin/vasopressin receptor family and will facilitate structure-guided development of new therapeutics.

scholarly journals Crystal structure of the human oxytocin receptor

2020 ◽  
Author(s):  
Yann Waltenspühl ◽  
Jendrik Schöppe ◽  
Janosch Ehrenmann ◽  
Lutz Kummer ◽  
Andreas Plückthun
Keyword(s):  
Crystal Structure ◽  
Preterm Labour ◽  
Peptide Hormone ◽  
Oxytocin Receptor ◽  
Oral Drug ◽  
Allosteric Modulator ◽  
Agonist Binding ◽  
Positive Allosteric Modulator ◽  
G Protein Coupled ◽  
Receptor Family

AbstractThe peptide hormone oxytocin modulates socioemotional behaviour and sexual reproduction via the centrally expressed oxytocin receptor (OTR) across several species. Here, we report the crystal structure of human OTR in complex with retosiban, a non-peptide antagonist developed as an oral drug for the prevention of preterm labour. Our structure reveals insights into the detailed interactions between the G-protein coupled receptor (GPCR) and an OTR-selective antagonist. The observation of an extrahelical cholesterol molecule, binding in an unexpected location between helix IV and V, provides a structural rationale for its allosteric effect and critical influence on OTR function. Furthermore, our structure in combination with experimental data allows the identification of a conserved neurohypophyseal receptor-specific coordination site for Mg2+ that acts as potent positive allosteric modulator for agonist binding. Together these results further our molecular understanding of the oxytocin/vasopressin receptor family and will facilitate structure-guided development of new therapeutics.

scholarly journals Adhesion GPCRs in Glioblastoma

2021 ◽  
Author(s):  
Gabriele Stephan ◽  
Niklas Ravn-Boess ◽  
Dimitris G Placantonakis
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
The Past ◽  
Novel Treatment ◽  
The Family ◽  
Health And Disease ◽  
Basic Biology ◽  
G Protein Coupled ◽  
Potential Use ◽  
Receptor Family

Abstract Members of the adhesion family of G protein-coupled receptors (GPCRs) have received attention for their roles in health and disease, including cancer. Over the past decade, several members of the family have been implicated in the pathogenesis of glioblastoma. Here, we discuss the basic biology of adhesion GPCRs and review in detail specific members of the receptor family with known functions in glioblastoma. Finally, we discuss the potential use of adhesion GPCRs as novel treatment targets in neuro-oncology.

scholarly journals Characterization of the G protein-coupled receptor family SREB across fish evolution

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Timothy S. Breton ◽  
William G. B. Sampson ◽  
Benjamin Clifford ◽  
Anyssa M. Phaneuf ◽  
Ilze Smidt ◽  
...  
Keyword(s):  
G Protein ◽  
Genomic Structure ◽  
Integrated Approach ◽  
Orphan Receptor ◽  
Specific Gene ◽  
Testicular Development ◽  
Brain Expression ◽  
And Function ◽  
G Protein Coupled ◽  
Receptor Family

AbstractThe SREB (Super-conserved Receptors Expressed in Brain) family of G protein-coupled receptors is highly conserved across vertebrates and consists of three members: SREB1 (orphan receptor GPR27), SREB2 (GPR85), and SREB3 (GPR173). Ligands for these receptors are largely unknown or only recently identified, and functions for all three are still beginning to be understood, including roles in glucose homeostasis, neurogenesis, and hypothalamic control of reproduction. In addition to the brain, all three are expressed in gonads, but relatively few studies have focused on this, especially in non-mammalian models or in an integrated approach across the entire receptor family. The purpose of this study was to more fully characterize sreb genes in fish, using comparative genomics and gonadal expression analyses in five diverse ray-finned (Actinopterygii) species across evolution. Several unique characteristics were identified in fish, including: (1) a novel, fourth euteleost-specific gene (sreb3b or gpr173b) that likely emerged from a copy of sreb3 in a separate event after the teleost whole genome duplication, (2) sreb3a gene loss in Order Cyprinodontiformes, and (3) expression differences between a gar species and teleosts. Overall, gonadal patterns suggested an important role for all sreb genes in teleost testicular development, while gar were characterized by greater ovarian expression that may reflect similar roles to mammals. The novel sreb3b gene was also characterized by several unique features, including divergent but highly conserved amino acid positions, and elevated brain expression in puffer (Dichotomyctere nigroviridis) that more closely matched sreb2, not sreb3a. These results demonstrate that SREBs may differ among vertebrates in genomic structure and function, and more research is needed to better understand these roles in fish.

Strategies to improve insulin delivery through oral route: A review

2021 ◽  
Vol 18 ◽  
Author(s):  
Rohini Bhattacharya ◽  
Asha P. Johnson ◽  
Shailesh T. ◽  
Mohamed Rahamathulla ◽  
Gangadharappa H. V.
Keyword(s):  
Diabetes Mellitus ◽  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Polymeric Micelles ◽  
Insulin Delivery ◽  
Peptide Hormone ◽  
Diabetes Mellitus Type 1 ◽  
Delivery Systems ◽  
Oral Insulin ◽  
Subcutaneous Route

: Diabetes mellitus is found to be among the most suffered and lethal diseases for mankind. Diabetes mellitus type-1 is caused by the demolition of pancreatic islets responsible for the secretion of insulin. Insulin is the peptide hormone (anabolic] that regulates the metabolism of carbohydrates, fats, and proteins. Upon the breakdown of the natural process of metabolism, the condition leads to hyperglycemia (increased blood glucose levels]. Hyperglycemia demands outsourcing of insulin. The subcutaneous route was found to be the most stable route of insulin administration but faces patient compliance problems. Oral Insulin delivery systems are the patient-centered and innovative novel drug delivery system, eliminating the pain caused by the subcutaneous route of administration. Insulin comes in contact across various barriers in the gastrointestinal tract, which has been discussed in detail in this review. The review describes about the different bioengineered formulations, including microcarriers, nanocarriers, Self-Microemulsifying drug delivery systems (SMEDDs), Self-Nanoemulsifying drug delivery systems (SNEDDs), polymeric micelles, cochleates, etc. Surface modification of the carriers is also possible by developing ligand anchored bioconjugates. A study on evaluation has shown that the carrier systems facilitate drug encapsulation without tampering the properties of insulin. Carrier-mediated transport by the use of natural, semi-synthetic, and synthetic polymers have shown efficient results in drug delivery by protecting insulin from harmful environment. This makes the formulation readily acceptable for a variety of populations. The present review focuses on the properties, barriers present in the GI tract, overcome the barriers, strategies to formulate oral insulin formulation by enhancing the stability and bioavailability of insulin.

Hydrogen and potassium regulation of (pro)renin processing and secretion

1994 ◽  
Vol 267 (1) ◽  
pp. F1-F12 ◽  
Author(s):  
J. A. King ◽  
J. C. Fray
Keyword(s):  
Diabetes Mellitus ◽  
Heart Disease ◽  
Surface Membrane ◽  
Endocrine System ◽  
Renin Secretion ◽  
Endocrine Disorders ◽  
K Channels ◽  
Human Renin ◽  
Cl Channels ◽  
H Channels

H and K ions play central roles in prorenin processing and secretion, and prorenin is abnormally expressed in H and K disorders. At the surface membrane of juxtaglomerular (JG) cells, K is sensed and regulated by K channels (coupled to Cl channels and activated by excess Ca), Na-K-adenosinetriphosphatase, and a KCl/H exchange transporter (regulated by Ca). In JG cell granular membrane, K flux is regulated by K channels and a KCl/H exchange transporter (activated by Ca). H channels and a H pump reside in the granular membrane, which maintain H concentration in the granular matrix at least two orders of magnitude greater than in cytosol. The H pump may also be responsible for maintaining the acidic matrix required for maximal prorenin processing to renin by prohormone convertase for human renin (PCren), the prorenin convertase. These molecules form the core of a chemiosmotic system, which appears to regulate both prorenin processing and renin secretion. Renin secretion and prorenin processing appear to be of more than causal significance in clinical disorders characterized by chemiosmotic imbalance. A critical review of the literature supports the following general conclusions. First, hyperrenin state defines the initial phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension. Second, low-renin syndrome defines the transition-to-establish phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension in which the key feature is renin secretory hyporesponsivity. Third, renin disorders are usually associated with other endocrine disorders (polyendocrinopathies types I, II, and III), suggesting that renin may be an important molecule in the processing of chemiosmotic forces. The key chemiosmotic molecules (K and H) are also important in the processing and export of most (if not all) hormones. Thus, by regulating K and H homeostasis, renin may regulate the endocrine system.

scholarly journals Generating FSH antagonists and agonists through immunization against FSH receptor N-terminal decapeptides

1999 ◽  
Vol 22 (2) ◽  
pp. 151-159 ◽  
Author(s):  
L Abdennebi ◽  
L Couture ◽  
D Grebert ◽  
E Pajot ◽  
R Salesse ◽  
...  
Keyword(s):  
Chinese Hamster ◽  
Biochemical Properties ◽  
Ovary Cell ◽  
Fsh Receptor ◽  
Female Mice ◽  
Specific Receptors ◽  
Ovary Cell Line ◽  
G Protein Coupled ◽  
Follicle Maturation ◽  
Receptor Family

Follicle-stimulating hormone (FSH) via interaction with G-protein coupled specific receptors plays a central role in the control of gametogenesis in mammals of both sexes. In females, FSH is crucial for follicle growth, follicle maturation and ovulation. FSH receptors, together with luteinizing hormone-chorionic gonadotropin and thyrotropin receptors belong to a subfamily of structurally related receptors within the seven transmembrane receptor family. Among several other regions, the N-terminus of these receptors is believed to be responsible for important specific hormone-receptor contact sites. Recombinant filamentous phages displaying at their surface three overlapping N-terminal decapeptides of the FSH receptor, peptides A18-27, B25-34 and C29-38 were constructed. Ewes and female mice were immunized against the three FSH receptor (FSHR) recombinant phages. Immunoglobulins purified from immunized animals were analyzed for their biochemical properties on a Chinese hamster ovary cell line expressing the porcine FSH receptor. AntiA and antiB immunoglobulins (IgGs) behave as antagonists for 125I-FSH binding and for FSH-dependent cAMP production, while antiC IgGs did not compete for hormone binding. By contrast, antibodies against the C29-38 peptide displayed FSH agonist activity and stimulated the FSH receptor, whereas antiA and antiB IgGs did not. Furthermore, when the FSHR phages were used as peptidic vaccines, they induced a reversible inhibition of ovulation rate in ewes, and impaired fertility in female mice.

Genetics of Endocrine Disorders and Diabetes Mellitus

2020 ◽  
pp. 315-345
Author(s):  
Bess Adkins Marshall ◽  
Abby Solomon Hollander
Keyword(s):  
Diabetes Mellitus ◽  
Endocrine Disorders

scholarly journals Thyroid hormones profile of patients with type 2 diabetes mellitus in Kano, Nigeria

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Mustapha Zainab Abubakar ◽  
Kabiru Abdulsalam ◽  
Isah A. Yahaya
Keyword(s):  
Diabetes Mellitus ◽  
Thyroid Dysfunction ◽  
Cross Sectional Study ◽  
Endocrine Disorders ◽  
Cross Sectional ◽  
Type 2 Dm ◽  
Type 2 Diabetics ◽  
Patients With Diabetes ◽  
Considerable Impact

Diabetes mellitus (DM) and thyroid disease are the two most common endocrine disorders in the general population. Several Studies have shown that thyroid dysfunction is common in patients with DM, and thyroid dysfunction have been found to have a considerable impact on the glycaemic control and often increases the risk of development of long-term complications in patients with diabetes mellitus. This study determined the prevalence of thyroid dysfunction in patients with type 2 DM in Kano, North-Western Nigeria. The study was a descriptive cross-sectional study conducted on 250 participants made up of 130 patients with type 2 DM and 120 apparently healthy non-diabetic controls. Questionnaires were used to collect information on bio data, medical history, duration of diagnosis of diabetes and type of treatment. Also, blood samples of the participants were collected and analyzed for fasting plasma glucose, fT3, fT4, and TSH. The results were interpreted using American Thyroid Associations’ criteria and the data was analyzed using the statistical software package, STATA version 20. Two hundred and thirty-four (93.6%) of the participants were euthyroid while sixteen (6.4%) were found to have various forms of thyroid dysfunction. The prevalence of thyroid dysfunction was 10% and 2.5% among type 2 diabetics and controls respectively. Among the type 2 DM patients with thyroid dysfunction, 38.5% had hypothyroidism. Thyroid dysfunction was found to be commoner among type 2 DM patients than non-diabetic individuals with hypothyroidism being the commonest disorder.

scholarly journals Endocrine Disorders in a Specialized Hospital in Guyana

2019 ◽  
pp. 30-31
Author(s):  
Yaquelin Gonzalez Ricardo ◽  
Yaritza Lopez Diaz ◽  
Ravendra Johnaton Dudnauth ◽  
Maritza Oliva Perez
Keyword(s):  
Diabetes Mellitus ◽  
Pituitary Tumors ◽  
Obstetric Care ◽  
Endocrine Disorders ◽  
Patients With Diabetes ◽  
Sheehan Syndrome ◽  
One Year ◽  
The One ◽  
Low Prevalence ◽  
Endocrinology Clinic

Background: Endocrine diseases are characterized by hormonal alterations (excess or defect). Due to the low prevalence (less than five case 5 / 10 000 inhabitants), a large number of them, qualify to be classified as rare diseases such as those of organs like: hypophysis, adrenal glands, gonads as well as some congenital thyroid diseases. Others like Diabetes are considering almost epidemic. Objective: To define the types of diseases observed in the only Endocrinology Clinic in Guyana. Methods: The diagnoses of all patients who attended the endocrinology clinic of the Georgetown Public Hospital Corporation from June 1, 2016 to May 31, 2017, were analyzed. Results: During the one year of this study, approximately 639 patients attended the endocrinology clinic. Of this, 178 patients had thyroid-related diseases with 80 of these having thyrotoxicosis, 49 having hypothyroidism followed by 110 patients with diabetes mellitus. Pituitary tumors were also diagnosed with 2 of acromegaly and 6 of prolactinomas. Cases of hypoadrenalism (n = 5), hypogonadism (n = 4), and pheochromocytoma (n = 6) were not rare; gonadal disease were also found in 17 patients. Thyroid disease was the most frequent diagnosis followed by diabetes mellitus. New emerging endocrine disorders such as hyperlipidemia (n = 1) were rare. Some persons attending the clinic were also noted to be overweight /obese however this was not the primary reason for joining the clinic. Traditional diseases such as Sheehan Syndrome have become rare due to improvements in Obstetric care. 

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