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2. Functional Gly297Ser Variant of the Physiological Dysglycemic Peptide Pancreastatin is a Novel Risk Factor for Cardiometabolic Disorders

Author

Allu, Prasanna K. R., primary, Kiranmayi, Malapaka, primary, Mukherjee, Sromona D., primary, Chirasani, Venkat R., primary, Garg, Richa, primary, Vishnuprabu, Durairajpandian, primary, Ravi, Sudesh, primary, Subramanian, Lakshmi, primary, Sahu, Bhavani S., primary, Iyer, Dhanya R., primary, Maghajoti, Sakthisree, primary, Sharma, Saurabh, primary, Ravi, Marimuthu S., primary, Khullar, Madhu, primary, Munirajan, Arasambattu K., primary, Gayen, Jiaur R., primary, Senapati, Sanjib, primary, Mullasari, Ajit S., primary, Mohan, Viswanathan, primary, Radha, Venkatesan, primary, Prasad, Sathyamangala V. Naga, primary, and Mahapatra, Nitish R., primary

Published
2021
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3. Functional Gly297Ser Variant of the Physiological Dysglycemic Peptide Pancreastatin Is a Novel Risk Factor for Cardiometabolic Disorders

Author

Allu, Prasanna K.R., primary, Kiranmayi, Malapaka, additional, Mukherjee, Sromona D., additional, Chirasani, Venkat R., additional, Garg, Richa, additional, Vishnuprabu, Durairajpandian, additional, Ravi, Sudesh, additional, Subramanian, Lakshmi, additional, Sahu, Bhavani S., additional, Iyer, Dhanya R., additional, Maghajothi, Sakthisree, additional, Sharma, Saurabh, additional, Ravi, Marimuthu S., additional, Khullar, Madhu, additional, Munirajan, Arasambattu K., additional, Gayen, Jiaur R., additional, Senapati, Sanjib, additional, Mullasari, Ajit S., additional, Mohan, Viswanathan, additional, Radha, Venkatesan, additional, Naga Prasad, Sathyamangala V., additional, and Mahapatra, Nitish R., additional

Published
2021
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6. Functional Gly297Ser Variant of the Physiological Dysglycemic Peptide Pancreastatin Is a Novel Risk Factor for Cardiometabolic Disorders.

Author

Allu, Prasanna K.R., Kiranmayi, Malapaka, Mukherjee, Sromona D., Chirasani, Venkat R., Garg, Richa, Vishnuprabu, Durairajpandian, Ravi, Sudesh, Subramanian, Lakshmi, Sahu, Bhavani S., Iyer, Dhanya R., Maghajothi, Sakthisree, Sharma, Saurabh, Ravi, Marimuthu S., Khullar, Madhu, Munirajan, Arasambattu K., Gayen, Jiaur R., Senapati, Sanjib, Mullasari, Ajit S., Mohan, Viswanathan, and Radha, Venkatesan

Subjects
PEPTIDES, TYPE 2 diabetes, MOLECULAR dynamics, GLUCOSE-regulated proteins, DIASTOLIC blood pressure, SINGLE nucleotide polymorphisms, HEMOGLOBINS, CARRIER proteins
Abstract

Pancreastatin (PST), a chromogranin A-derived potent physiological dysglycemic peptide, regulates glucose/insulin homeostasis. We have identified a nonsynonymous functional PST variant (p.Gly297Ser; rs9658664) that occurs in a large section of human populations. Association analysis of this single nucleotide polymorphism with cardiovascular/metabolic disease states in Indian populations (n = 4,300 subjects) displays elevated plasma glucose, glycosylated hemoglobin, diastolic blood pressure, and catecholamines in Gly/Ser subjects as compared with wild-type individuals (Gly/Gly). Consistently, the 297Ser allele confers an increased risk (∼1.3-1.6-fold) for type 2 diabetes/hypertension/coronary artery disease/metabolic syndrome. In corroboration, the variant peptide (PST-297S) displays gain-of-potency in several cellular events relevant for cardiometabolic disorders (e.g., increased expression of gluconeogenic genes, increased catecholamine secretion, and greater inhibition of insulin-stimulated glucose uptake) than the wild-type peptide. Computational docking analysis and molecular dynamics simulations show higher affinity binding of PST-297S peptide with glucose-regulated protein 78 (GRP78) and insulin receptor than the wild-type peptide, providing a mechanistic basis for the enhanced activity of the variant peptide. In vitro binding assays validate these in silico predictions of PST peptides binding to GRP78 and insulin receptor. In conclusion, the PST 297Ser allele influences cardiovascular/metabolic phenotypes and emerges as a novel risk factor for type 2 diabetes/hypertension/coronary artery disease in human populations. [ABSTRACT FROM AUTHOR]

Published
2022
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7. Catestatin Gly364Ser Variant Alters Systemic Blood Pressure and the Risk for Hypertension in Human Populations via Endothelial Nitric Oxide Pathway

Author

Kiranmayi, Malapaka, primary, Chirasani, Venkat R., additional, Allu, Prasanna K.R., additional, Subramanian, Lakshmi, additional, Martelli, Elizabeth E., additional, Sahu, Bhavani S., additional, Vishnuprabu, Durairajpandian, additional, Kumaragurubaran, Rathnakumar, additional, Sharma, Saurabh, additional, Bodhini, Dhanasekaran, additional, Dixit, Madhulika, additional, Munirajan, Arasambattu K., additional, Khullar, Madhu, additional, Radha, Venkatesan, additional, Mohan, Viswanathan, additional, Mullasari, Ajit S., additional, Naga Prasad, Sathyamangla V., additional, Senapati, Sanjib, additional, and Mahapatra, Nitish R., additional

Published
2016
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9. p53 gene mutations in oral carcinomas from India

Author

Munirajan, Arasambattu K., primary, Tutsumi-Ishii, Yuko, additional, Mohanprasad, Bagavathi K. C., additional, Hirano, Yasumasa, additional, Munakata, Nobuo, additional, Shanmugam, Govindaswamy, additional, and Tsuchida, Nobuo, additional

Published
1996
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