Tapan Behl1, Amit Gupta2, Aayush Sehgal2, Sanchay Sharma2, Sukhbir Singh2, Neelam Sharma2, Camelia Cristina Diaconu3,4, Abbas Rahdar5, Abdul Hafeez6, Saurabh Bhatia7,8, Ahmed Al-Harrasi8, Simona Bungau9. 1. Chitkara College of Pharmacy, Chitkara University, Punjab, India. tapanbehl31@gmail.com. 2. Chitkara College of Pharmacy, Chitkara University, Punjab, India. 3. Internal Medicine Department, Clinical Emergency Hospital of Bucharest, Bucharest, Romania. 4. Department 5, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania. 5. Department of Physics, University of Zabol, Zabol, Iran. 6. Glocal School of Pharmacy, Glocal University, Mirzapur, Uttar Pradesh, India. 7. Amity Institute of Pharmacy, Amity University, Haryana, India. 8. Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Oman. 9. Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania.
Abstract
OBJECTIVE: Type 2 diabetes (T2D) is one of the centenarian metabolic disorders and is considered as a stellar and leading health issue worldwide. According to the International Diabetes Federation (IDF) Diabetes Atlas and National Diabetes Statistics, the number of diabetic patients will increase at an exponential rate from 463 to 700 million by the year 2045. Thus, there is a great need for therapies targeting functions that can help in maintaining the homeostasis of glucose levels and improving insulin sensitivity. 5' adenosine monophosphate-activated protein kinase (AMPK) activation, by various direct and indirect factors, might help to overcome the hurdles (like insulin resistance) associated with the conventional approach. MATERIALS AND RESULTS: A thorough review and analysis was conducted using various database including MEDLINE and EMBASE databases, with Google scholar using various keywords. This extensive review concluded that various drugs (plant-based, synthetic indirect/direct activators) are available, showing tremendous potential in maintaining the homeostasis of glucose and lipid metabolism, without causing insulin resistance, and improving insulin sensitivity. Moreover, these drugs have an effect against diabetes and are therapeutically beneficial in the treatment of diabetes-associated complications (neuropathy and nephropathy) via mechanism involving inhibition of nuclear translocation of SMAD4 (SMAD family member) expression and association with peripheral nociceptive neurons mediated by AMPK. CONCLUSION: From the available information, it may be concluded that various indirect/direct activators show tremendous potential in maintaining the homeostasis of glucose and lipid metabolism, without resulting in insulin resistance, and may improve insulin sensitivity, as well. Therefore, in a nut shell, it may be concluded that the regulation of APMK functions by various direct/indirect activators may bring promising results. These activators may emerge as a novel therapy in diabetes and its associated complications.
OBJECTIVE: Type 2 diabetes (T2D) is one of the centenarian metabolic disorders and is considered as a stellar and leading health issue worldwide. According to the International Diabetes Federation (IDF) Diabetes Atlas and National Diabetes Statistics, the number of diabetic patients will increase at an exponential rate from 463 to 700 million by the year 2045. Thus, there is a great need for therapies targeting functions that can help in maintaining the homeostasis of glucose levels and improving insulin sensitivity. 5' adenosine monophosphate-activated protein kinase (AMPK) activation, by various direct and indirect factors, might help to overcome the hurdles (like insulin resistance) associated with the conventional approach. MATERIALS AND RESULTS: A thorough review and analysis was conducted using various database including MEDLINE and EMBASE databases, with Google scholar using various keywords. This extensive review concluded that various drugs (plant-based, synthetic indirect/direct activators) are available, showing tremendous potential in maintaining the homeostasis of glucose and lipid metabolism, without causing insulin resistance, and improving insulin sensitivity. Moreover, these drugs have an effect against diabetes and are therapeutically beneficial in the treatment of diabetes-associated complications (neuropathy and nephropathy) via mechanism involving inhibition of nuclear translocation of SMAD4 (SMAD family member) expression and association with peripheral nociceptive neurons mediated by AMPK. CONCLUSION: From the available information, it may be concluded that various indirect/direct activators show tremendous potential in maintaining the homeostasis of glucose and lipid metabolism, without resulting in insulin resistance, and may improve insulin sensitivity, as well. Therefore, in a nut shell, it may be concluded that the regulation of APMK functions by various direct/indirect activators may bring promising results. These activators may emerge as a novel therapy in diabetes and its associated complications.
Authors: Rebecca J Ford; Morgan D Fullerton; Stephen L Pinkosky; Emily A Day; John W Scott; Jonathan S Oakhill; Adam L Bujak; Brennan K Smith; Justin D Crane; Regje M Blümer; Katarina Marcinko; Bruce E Kemp; Hertzel C Gerstein; Gregory R Steinberg Journal: Biochem J Date: 2015-05-15 Impact factor: 3.857
Authors: David M Nathan; John B Buse; Mayer B Davidson; Ele Ferrannini; Rury R Holman; Robert Sherwin; Bernard Zinman Journal: Diabetes Care Date: 2008-10-22 Impact factor: 17.152