Effect of Intermittent Calorie Restriction on NAFLD Patients With Disorders of Glucose Metabolism

We evaluated the effects of 8 mo of calorie restriction [CR: 60% of ad libitum (AL) food intake] on glucose uptake by 14 tissues in unanesthetized, adult (12 mo) F344×BN rats. Glucose metabolism was assessed by the 2-[3H]deoxyglucose tracer technique at 1500 or 2100. Despite an ∼60% decline in insulinemia with CR, plasma 2-[3H]deoxyglucose clearance for CR was greater than for AL at both times. A small, CR-related decrease in glucose metabolic index ([Formula: see text]) occurred only at 1500 in the spleen and heart, and this decrease was reversed at 2100. In some tissues (cerebellum, lung, kidney, soleus, and diaphragm),[Formula: see text] was unaffected by diet, regardless of time. In the other tissues (brown fat, 3 white fat pads, epitrochlearis, plantaris, and gastrocnemius),[Formula: see text] was higher or tended to be higher for CR vs. AL at one or both times. These findings indicate that 8 mo of CR did not cause a continuous reduction in in vivo glucose uptake by any tissue studied, and, in several insulin-sensitive tissues, glucose uptake was at times greater for CR vs. AL rats.

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mTOR Inhibitor Therapy and Metabolic Consequences: Where Do We Stand?

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/2640342 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 15

Author(s):

Aleksandra Kezic ◽

Ljiljana Popovic ◽

Katarina Lalic

Keyword(s):

Protein Kinase ◽

Glucose Metabolism ◽

Calorie Restriction ◽

Mtor Inhibitor ◽

Hepatic Glucose Production ◽

Mtor Inhibitors ◽

Glucose Production ◽

Metabolic Effects ◽

Solid Organ ◽

Amp Activated Protein Kinase

mTOR (mechanistic target of rapamycin) protein kinase acts as a central integrator of nutrient signaling pathways. Besides the immunosuppressive role after solid organ transplantations or in the treatment of some cancers, another promising role of mTOR inhibitor as an antiaging therapeutic has emerged in the recent years. Acute or intermittent rapamycin treatment has some resemblance to calorie restriction in metabolic effects such as an increased insulin sensitivity. However, the chronic inhibition of mTOR by macrolide rapamycin or other rapalogs has been associated with glucose intolerance and insulin resistance and may even provoke type II diabetes. These metabolic adverse effects limit the use of mTOR inhibitors. Metformin is a widely used drug for the treatment of type 2 diabetes which activates AMP-activated protein kinase (AMPK), acting as calorie restriction mimetic. In addition to the glucose-lowering effect resulting from the decreased hepatic glucose production and increased glucose utilization, metformin induces fatty acid oxidations. Here, we review the recent advances in our understanding of the metabolic consequences regarding glucose metabolism induced by mTOR inhibitors and compare them to the metabolic profile provoked by metformin use. We further suggest metformin use concurrent with rapalogs in order to pharmacologically address the impaired glucose metabolism and prevent the development of new-onset diabetes mellitus after solid organ transplantations induced by the chronic rapalog treatment.

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Impaired glucose metabolism and altered gut microbiome despite calorie restriction of ob/ob mice

Animal Microbiome ◽

10.1186/s42523-019-0007-1 ◽

2019 ◽

Vol 1 (1) ◽

Author(s):

Alireza Kashani ◽

Asker Daniel Brejnrod ◽

Chunyu Jin ◽

Timo Kern ◽

Andreas Nygaard Madsen ◽

...

Keyword(s):

Glucose Metabolism ◽

Calorie Restriction ◽

Gut Microbiome ◽

Impaired Glucose Metabolism

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Calorie Restriction Mimetics: Upstream-Type Compounds for Modulating Glucose Metabolism

Nutrients ◽

10.3390/nu10121821 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1821 ◽

Cited By ~ 20

Author(s):

Hideya Shintani ◽

Tomoya Shintani ◽

Hisashi Ashida ◽

Masashi Sato

Keyword(s):

Glucose Metabolism ◽

Calorie Restriction ◽

Intracellular Signaling ◽

Current Knowledge ◽

Signaling Proteins ◽

Human Lifespan ◽

Sodium Glucose Cotransporter ◽

Metabolism Inhibition ◽

Definition Of

Calorie restriction (CR) can prolong the human lifespan, but enforcing long-term CR is difficult. Therefore, a compound that reproduces the effect of CR without CR is needed. In this review, we summarize the current knowledge on compounds with CR mimetic (CRM) effects. More than 10 compounds have been listed as CRMs, some of which are conventionally categorized as upstream-type CRMs showing glycolytic inhibition, while the others are categorized as downstream-type CRMs that regulate or genetically modulate intracellular signaling proteins. Among these, we focus on upstream-type CRMs and propose their classification as compounds with energy metabolism inhibition effects, particularly glucose metabolism modulation effects. The upstream-type CRMs reviewed include chitosan, acarbose, sodium-glucose cotransporter 2 inhibitors, and hexose analogs such as 2-deoxy-d-glucose, d-glucosamine, and d-allulose, which show antiaging and longevity effects. Finally, we discuss the molecular definition of upstream-type CRMs.

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Calorie Restriction Mimetics: Upstream-Type Compounds for Modulating Glucose Metabolism

10.20944/preprints201811.0179.v1 ◽

2018 ◽

Author(s):

Hideya Shintani ◽

Tomoya Shintani ◽

Hisashi Ashida ◽

Masashi Sato

Keyword(s):

Energy Metabolism ◽

Glucose Metabolism ◽

Calorie Restriction ◽

Intracellular Signaling ◽

Current Knowledge ◽

Signaling Proteins ◽

Sodium Glucose Cotransporter ◽

Metabolism Inhibition ◽

Definition Of

Calorie restriction (CR) has been shown to prolong the lifespan of humans, but enforcing long-term CR is difficult. Therefore, a compound that reproduces the effect of CR without CR is needed. In this review, we summarize the current knowledge on compounds with CR mimetic (CRM) effects. More than 10 compounds have been listed as CRMs, some of which are conventionally categorized as upstream-type CRMs showing glycolytic inhibition while the others are categorized as downstream-type CRMs that regulate or genetically modulate intracellular signaling proteins. Among these, we focus on upstream-type CRMs and propose their classification as compounds with energy metabolism inhibition effects, particularly glucose metabolism modulation effects. The upstream-type CRMs reviewed include chitosan, acarbose, sodium-glucose cotransporter 2 inhibitors, and hexose analogs such as 2-deoxy-D-glucose, D-glucosamine, and D-allulose, which show anti-aging and longevity effects. Finally, we discuss the molecular definition of upstream-type CRMs.

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