Neil B. Ruderman
Boston University
Publications 293
#1Katherine Allen (BU: Boston University)H-Index: 2
#2Kimberly A. Coughlan (BU: Boston University)H-Index: 6
Last.Asish K. Saha (BU: Boston University)H-Index: 51
view all 6 authors...
Abstract AMP-activated protein kinase (AMPK) is an enzyme crucial in cellular metabolism found to be inhibited in many metabolic diseases including type 2 diabetes. Thiazolidinediones (TZDs) are a class of anti-diabetic drug known to activate AMPK through increased phosphorylation at Thr 172 , however there has been no research to date on whether they have any effect on inhibition of AMPK's lesser known site of inhibition, Ser 485/491 . HepG2 cells were treated with troglitazone and phosphorylat...
#1Camille AttanéH-Index: 8
#2Marie-Line PeyotH-Index: 17
Last.Marc PrentkiH-Index: 68
view all 16 authors...
Aims/hypothesis To directly assess the role of beta cell lipolysis in insulin secretion and whole-body energy homeostasis, inducible beta cell-specific adipose triglyceride lipase (ATGL)-deficient (B-Atgl-KO) mice were studied under normal diet (ND) and high-fat diet (HFD) conditions.
12 CitationsSource
#1Karen A. Weikel (BU: Boston University)H-Index: 11
#2Jose M. Cacicedo (BU: Boston University)H-Index: 17
Last.Yasuo Ido (BU: Boston University)H-Index: 35
view all 4 authors...
High concentrations of glucose and palmitate increase endothelial cell inflammation and apoptosis, events that often precede atherogenesis. They may do so by decreasing basal autophagy and AMP-activated protein kinase (AMPK) activity, although the mechanisms by which this occurs are not clear. Decreased function of the lysosome, an organelle required for autophagy and AMPK, have been associated with hyperactivity of glycogen synthase kinase 3β (GSK3β). To determine whether GSK3β affects nutrient...
7 CitationsSource
#1X. Julia XuH-Index: 11
Last.Neil B. RudermanH-Index: 91
view all 9 authors...
Objective: Excess nutrients can cause insulin resistance in skeletal muscle in vivo. However, the response of white adipose tissue is less clear. In a chronic glucose infusion model (1 and 4 days), distinct adaptations in muscle and white adipose tissue have been described. Muscle developed sustained insulin resistance after 1 day of glucose infusion but adipose tissue did not. Exactly what distinguishes adipose tissue from muscle in response to glucose oversupply remains to be determined. The a...
#1Karen A. Weikel (BU: Boston University)H-Index: 11
#2Neil B. Ruderman (BU: Boston University)H-Index: 91
Last.Jose M. Cacicedo (BU: Boston University)H-Index: 17
view all 3 authors...
AMP-activated protein kinase (AMPK) plays a critical role both in sensing and regulating cellular energy state. In experimental animals, its activation has been shown to reduce the risk of obesity and diabetes-related co-morbidities such as insulin resistance, the metabolic syndrome and atherosclerotic cardiovascular disease. However, in humans, AMPK activation alone often does not completely resolve these conditions. Thus, an improved understanding of AMPK action and regulation in metabolic and...
22 CitationsSource
#1Émilie PepinH-Index: 9
#2Anfal Al-Mass (McGill University)H-Index: 6
Last.Marie-Line PeyotH-Index: 17
view all 12 authors...
Diet induced obese (DIO) mice can be stratified according to their weight gain in response to high fat diet as low responders (LDR) and high responders (HDR). This allows the study of β-cell failure and the transitions to prediabetes (LDR) and early diabetes (HDR). C57BL/6N mice were fed for 8 weeks with a normal chow diet (ND) or a high fat diet and stratified as LDR and HDR. Freshly isolated islets from ND, LDR and HDR mice were studied ex-vivo for mitochondrial metabolism, AMPK activity and s...
13 CitationsSource
#1Kimberly A. Coughlan (BU: Boston University)H-Index: 6
#2Rudy J. Valentine (Iowa State University)H-Index: 4
Last.Asish K. Saha (BMC: Boston Medical Center)H-Index: 51
view all 8 authors...
AMP-activated protein kinase (AMPK) is an energy-sensing enzyme whose activity is inhibited in settings of insulin resistance. Exposure to a high glucose concentration has recently been shown to increase phosphorylation of AMPK at Ser(485/491) of its α1/α2 subunit; however, the mechanism by which it does so is not known. Diacylglycerol (DAG), which is also increased in muscle exposed to high glucose, activates a number of signaling molecules including protein kinase (PK)C and PKD1. We sought to ...
19 CitationsSource
#1Christopher J. Nolan (ANU: Australian National University)H-Index: 26
#2Neil B. Ruderman (BMC: Boston Medical Center)H-Index: 91
Last.Marc Prentki (UdeM: Université de Montréal)H-Index: 68
view all 5 authors...
We thank Taegtmeyer et al. (1) and Zaccardi et al. (2) for their insightful comments on our recent article (3). Both are very supportive of our view that insulin resistance (IR) has a protective role against insulin-mediated metabolic stress in overweight and obese patients with type 2 diabetes (T2D). Our article is similar to several recent articles (4–7). With this consolidation of views, clinicians should consider the implications of this concept for their patients with obesity-associated T2D...
2 CitationsSource
#1X. Julia Xu (BU: Boston University)H-Index: 11
#2Caroline M. Apovian (BU: Boston University)H-Index: 48
Last.Neil B. Ruderman (BU: Boston University)H-Index: 91
view all 6 authors...
Morbidly obese individuals are predisposed to a wide range of disorders, including type 2 diabetes, atherosclerotic cardiovascular disease, fatty liver disease, and certain cancers. Remarkably, all of these disorders can be improved or prevented by Roux-en-Y gastric bypass (RYGB) surgery. We have reported that decreased AMPK activity, together with increased oxidative stress and inflammation in adipose tissue, is associated with insulin resistance in morbidly obese bariatric surgery patients. In...
28 CitationsSource
#1Kimberly A. Coughlan (BMC: Boston Medical Center)H-Index: 6
#2Thomas W. Balon (BMC: Boston Medical Center)H-Index: 24
Last.Asish K. Saha (BMC: Boston Medical Center)H-Index: 51
view all 10 authors...
We have previously shown that incubation for 1h with excess glucose or leucine causes insulin resistance in rat extensor digitorum longus (EDL) muscle by inhibiting AMP-activated protein kinase (AMPK). To examine the events that precede and follow these changes, studies were performed in rat EDL incubated with elevated levels of glucose or leucine for 30min-2h. Incubation in high glucose (25mM) or leucine (100μM) significantly diminished AMPK activity by 50% within 30min, with further decreases ...
15 CitationsSource