scholarly journals γ-PGA-Rich Chungkookjang, Short-Term Fermented Soybeans: Prevents Memory Impairment by Modulating Brain Insulin Sensitivity, Neuro-Inflammation, and the Gut–Microbiome–Brain Axis

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 221
Author(s):  
Do-Youn Jeong ◽  
Myeong Seon Ryu ◽  
Hee-Jong Yang ◽  
Sunmin Park
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Gut Microbiome ◽  
Memory Impairment ◽  
Memory Function ◽  
Bacillus Species ◽  
Fermented Foods ◽  
Short Term ◽  
Brain Insulin ◽  
Brain Insulin Resistance

Fermented soybean paste is an indigenous food for use in cooking in East and Southeast Asia. Korea developed and used its traditional fermented foods two thousand years ago. Chungkookjang has unique characteristics such as short-term fermentation (24–72 h) without salt, and fermentation mostly with Bacilli. Traditionally fermented chungkookjang (TFC) is whole cooked soybeans that are fermented predominantly by Bacillus species. However, Bacillus species are different in the environment according to the regions and seasons due to the specific bacteria. Bacillus species differently contribute to the bioactive components of chungkookjang, resulting in different functionalities. In this review, we evaluated the production process of poly-γ-glutamic acid (γ-PGA)-rich chungkookjang fermented with specific Bacillus species and their effects on memory function through the modulation of brain insulin resistance, neuroinflammation, and the gut–microbiome–brain axis. Bacillus species were isolated from the TFC made in Sunchang, Korea, and they included Bacillus (B.) subtilis, B. licheniformis, and B. amyloliquefaciens. Chungkookjang contains isoflavone aglycans, peptides, dietary fiber, γ-PGA, and Bacillus species. Chungkookjangs made with B. licheniformis and B. amyloliquefaciens have higher contents of γ-PGA, and they are more effective for improving glucose metabolism and memory function. Chungkookjang has better efficacy for reducing inflammation and oxidative stress than other fermented soy foods. Insulin sensitivity is improved, not only in systemic organs such as the liver and adipose tissues, but also in the brain. Chungkookjang intake prevents and alleviates memory impairment induced by Alzheimer’s disease and cerebral ischemia. This review suggests that the intake of chungkookjang (20–30 g/day) rich in γ-PGA acts as a synbiotic in humans and promotes memory function by suppressing brain insulin resistance and neuroinflammation and by modulating the gut–microbiome–brain axis.

scholarly journals Dipeptidyl peptidase 4 inhibitor improves brain insulin sensitivity, but fails to prevent cognitive impairment in orchiectomy obese rats

2015 ◽  
Vol 226 (2) ◽  
pp. M1-M11 ◽  
Author(s):  
Hiranya Pintana ◽  
Wanpitak Pongkan ◽  
Wasana Pratchayasakul ◽  
Nipon Chattipakorn ◽  
Siriporn C Chattipakorn
Keyword(s):  
Insulin Resistance ◽  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Insulin Sensitivity ◽  
Cognitive Decline ◽  
Hippocampal Synaptic Plasticity ◽  
Brain Insulin ◽  
Obese Rats ◽  
Brain Insulin Resistance ◽  
Brain Mitochondrial Function

It is unclear whether the dipeptidyl peptidase 4 (DPP4) inhibitor can counteract brain insulin resistance, brain mitochondrial dysfunction, impairment of hippocampal synaptic plasticity and cognitive decline in testosterone-deprived obese rats. We hypothesized that DPP4 inhibitor vildagliptin improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function and hippocampal synaptic plasticity. Thirty male Wistar rats received either a sham-operated (S, n=6) or bilateral orchiectomy (ORX, n=24). ORX rats were divided into two groups and fed with either a normal diet (ND (NDO)) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (n=6/subgroup) to receive either a vehicle or vildagliptin (3 mg/kg per day, p.o.) for 4 weeks. After treatment, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity and brain mitochondrial function were determined in each rat. We found that HFO rats exhibited peripheral and brain insulin resistance, brain mitochondrial dysfunction, impaired hippocampal synaptic plasticity and cognitive decline. NDO rats did not develop peripheral and brain insulin resistance. However, impaired hippocampal synaptic plasticity and cognitive decline occurred. Vildagliptin significantly improved peripheral insulin sensitivity, restored brain insulin sensitivity and decreased brain mitochondrial reactive oxygen species production in HFO rats. However, vildagliptin did not restore hippocampal synaptic plasticity and cognitive function in both NDO and HFO rats. These findings suggest that vildagliptin could not counteract the impairment of hippocampal synaptic plasticity and cognitive decline in testosterone-deprived subjects, despite its effects on improved peripheral and brain insulin sensitivity as well as brain mitochondrial function.

scholarly journals Empagliflozin Improves Insulin Sensitivity of the Hypothalamus in Humans With Prediabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial

2021 ◽  
Author(s):  
Stephanie Kullmann ◽  
Julia Hummel ◽  
Robert Wagner ◽  
Corinna Dannecker ◽  
Andreas Vosseler ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Sglt2 Inhibitors ◽  
Whole Body ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Brain Insulin ◽  
Sglt2 Inhibition ◽  
Brain Insulin Resistance

<b>Objective:</b> Insulin action in the human brain reduces food intake, improves whole-body insulin sensitivity, and modulates body fat mass and its’ distribution. Obesity and type 2 diabetes are often associated with brain insulin resistance, resulting in impaired brain-derived modulation of peripheral metabolism. So far, no pharmacological treatment for brain insulin resistance has been established. Since SGLT2 inhibitors lowers glucose levels and modulate energy metabolism, we hypothesized that SGLT2 inhibition may be a pharmacological approach to reverse brain insulin resistance. <p><b>Research Design and Methods:</b> In this randomized, double-blind, placebo-controlled clinical trial, 40 patients (mean ± SD; age: 60 ± 9 years; BMI: 31.5 ± 3.8 kg/m²) with prediabetes were randomized to receive 25 mg empagliflozin qd or placebo. Before and after 8 weeks of treatment, brain insulin sensitivity was assessed by functional MRI combined with intranasal administration of insulin to the brain.</p> <p><b>Results:</b> We identified a significant interaction between time and treatment in the hypothalamic response to insulin. Post hoc analyses revealed that only empagliflozin treated patients experienced increased hypothalamic insulin responsiveness. Hypothalamic insulin action significantly mediated empagliflozin-induced decrease in fasting glucose and liver fat.</p> <p><b>Conclusions:</b> Our results corroborate insulin resistance of the hypothalamus in humans with prediabetes. Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity; a favorable response that could contribute to the beneficial effects of SGLT2 inhibitors. Our findings position SGLT2 inhibition as the first pharmacological approach to reverse brain insulin resistance, with potential benefits for adiposity and whole-body metabolism.</p>

scholarly journals Empagliflozin Improves Insulin Sensitivity of the Hypothalamus in Humans With Prediabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial

2021 ◽  
Author(s):  
Stephanie Kullmann ◽  
Julia Hummel ◽  
Robert Wagner ◽  
Corinna Dannecker ◽  
Andreas Vosseler ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Sglt2 Inhibitors ◽  
Whole Body ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Brain Insulin ◽  
Sglt2 Inhibition ◽  
Brain Insulin Resistance

<b>Objective:</b> Insulin action in the human brain reduces food intake, improves whole-body insulin sensitivity, and modulates body fat mass and its’ distribution. Obesity and type 2 diabetes are often associated with brain insulin resistance, resulting in impaired brain-derived modulation of peripheral metabolism. So far, no pharmacological treatment for brain insulin resistance has been established. Since SGLT2 inhibitors lowers glucose levels and modulate energy metabolism, we hypothesized that SGLT2 inhibition may be a pharmacological approach to reverse brain insulin resistance. <p><b>Research Design and Methods:</b> In this randomized, double-blind, placebo-controlled clinical trial, 40 patients (mean ± SD; age: 60 ± 9 years; BMI: 31.5 ± 3.8 kg/m²) with prediabetes were randomized to receive 25 mg empagliflozin qd or placebo. Before and after 8 weeks of treatment, brain insulin sensitivity was assessed by functional MRI combined with intranasal administration of insulin to the brain.</p> <p><b>Results:</b> We identified a significant interaction between time and treatment in the hypothalamic response to insulin. Post hoc analyses revealed that only empagliflozin treated patients experienced increased hypothalamic insulin responsiveness. Hypothalamic insulin action significantly mediated empagliflozin-induced decrease in fasting glucose and liver fat.</p> <p><b>Conclusions:</b> Our results corroborate insulin resistance of the hypothalamus in humans with prediabetes. Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity; a favorable response that could contribute to the beneficial effects of SGLT2 inhibitors. Our findings position SGLT2 inhibition as the first pharmacological approach to reverse brain insulin resistance, with potential benefits for adiposity and whole-body metabolism.</p>

Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Sunmin Park ◽  
Sunna Kang ◽  
Da Sol Kim
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Insulin Signaling ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Memory Function ◽  
Amyloid Β ◽  
Impaired Memory ◽  
Ca1 Region ◽  
Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

P2-107: Brain Insulin Resistance and Alzheimer's Disease Neuropathology Among Older Autopsied Persons With and Without Diabetes

2016 ◽  
Vol 12 ◽  
pp. P653-P653
Author(s):  
Rexford S. Ahima ◽  
Ana W. Capuano ◽  
Julie A. Schneider ◽  
David A. Bennett ◽  
Steven E. Arnold ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Brain Insulin ◽  
Brain Insulin Resistance

Insulin resistance caused by amylin in conscious rats is independent of induced hypocalcemia and fades during long-term exposure

1993 ◽  
Vol 129 (4) ◽  
pp. 360-365 ◽  
Author(s):  
Clemens Fürnsinn ◽  
Peter Nowotny ◽  
Michael Roden ◽  
Madeleine Rohac ◽  
Thomas Pieber ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Tolerance Test ◽  
Zucker Rats ◽  
Control Group ◽  
Short Term ◽  
Euglycemic Hyperinsulinemic Clamp

To compare the effect of short- vs long-term amylin infusion on insulin sensitivity, glucose tolerance and serum calcemia, euglycemic-hyperinsulinemic clamp (26 pmol·kg−1·min−1) and glucose tolerance tests (2.4 mmol/kg over 30 min) were performed in lean Zucker rats. Three infusion protocols were employed: control group: 24 h of iv saline; short-term amylin exposure: 22 h of iv saline followed by 2 h of iv amylin (20 μg/h); long-term amylin exposure: 24 h of iv amylin (20 μg/h). Insulin resistance was induced by short-term amylin infusion during euglycemic clamping, as shown by a 41% decrease in space-corrected glucose infusion rates (μmol·kg−1·min−1; control group, 106.0±15.0; short-term iv amylin, 62.7±15.0; p<0.00 5). After long-term amylin exposure, insulin sensitivity was identical to control values (109.9±6.7). This fading action of amylin was confirmed by data from the glucose tolerance test, demonstrating glucose intolerance after short- but not after long-term amylin exposure. Serum calcium concentration decreased during short-term (2 h) amylin infusion (from 2.52±0.15 to 2.09±0.12 mmol/l; p<0.01) and hypocalcemia of a similar extent also was present after 22 h and 24 h of amylin exposure (2.10±0.09 and 2.04±0.14 mmol/l, respectively). The data demonstrate that short-term amylin infusion induces insulin resistance and glucose intolerance, both of which vanish during long-term (>22 h) amylin exposure, being apparently independent of induced hypocalcemia.

Thinking about brain insulin resistance

2018 ◽  
Vol 12 (6) ◽  
pp. 1091-1094 ◽  
Author(s):  
Reem M. Al Haj Ahmad ◽  
Hayder A. Al-Domi
Keyword(s):  
Insulin Resistance ◽  
Brain Insulin ◽  
Brain Insulin Resistance
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