The impact of low and no-caloric sweeteners on glucose absorption, incretin secretion, and glucose tolerance

The consumption of non-nutritive, low, or no-calorie sweeteners (LCS) is increasing globally. Previously thought to be physiologically inert, there is a growing body of evidence that LCS not only provide a sweet taste but may also elicit metabolic effects in the gastrointestinal tract. This review provides a brief overview of the chemical and receptor-binding properties and effects on chemosensation of different LCS but focuses on the extent to which LCS stimulates glucose transport, incretin and insulin secretion, and effects on glucose tolerance. Aspartame and sucralose both bind to a similar region of the sweet receptor. For sucralose, the data are contradictory regarding effects on glucose tolerance in humans and may depend on the food or beverage matrix and the duration of administration, as suggested by longer term rodent studies. For aspartame, there are fewer data. On the other hand, acesulfame-potassium (Ace-K) and saccharin have similar binding characteristics to each other but, while Ace-K may increase incretin secretion and glucose responses in humans, there are no data on saccharin except in rats, which show impaired glucose tolerance after chronic administration. Additional research, particularly of the effects of chronic consumption, is needed to provide concrete evidence for beneficial or detrimental effects of LCS on blood glucose regulation in humans.

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Chronic PYY3–36 treatment promotes fat oxidation and ameliorates insulin resistance in C57BL6 mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00239.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. E238-E245 ◽

Cited By ~ 46

Author(s):

Anita M. van den Hoek ◽

Annemieke C. Heijboer ◽

Peter J. Voshol ◽

Louis M. Havekes ◽

Johannes A. Romijn ◽

...

Keyword(s):

Insulin Sensitivity ◽

Energy Metabolism ◽

Food Intake ◽

Statistical Significance ◽

Chronic Administration ◽

Metabolic Effects ◽

Whole Body ◽

Glucose Disposal ◽

Glucose Turnover ◽

The Impact

PYY3–36 is a gut-derived hormone acting on hypothalamic nuclei to inhibit food intake. We recently showed that PYY3–36 acutely reinforces insulin action on glucose disposal in mice. We aimed to evaluate effects of PYY3–36 on energy metabolism and the impact of chronic PYY3–36 treatment on insulin sensitivity. Mice received a single injection of PYY3–36 or were injected once daily for 7 days, and energy metabolism was subsequently measured in a metabolic cage. Furthermore, the effects of chronic PYY3–36 administration (continuous and intermittent) on glucose turnover were determined during a hyperinsulinemic-euglycemic clamp. PYY3–36 inhibited cumulative food intake for 30 min of refeeding after an overnight fast (0.29 ± 0.04 vs. 0.56 ± 0.12 g, P = 0.036) in an acute setting, but not after 7 days of daily dosing. Body weight, total energy expenditure, and physical activity were not affected by PYY3–36. However, it significantly decreased the respiratory quotient. Both continuous and intermittent PYY3–36 treatment significantly enhanced insulin-mediated whole body glucose disposal compared with vehicle treatment (81.2 ± 6.2 vs. 77.1 ± 5.2 vs. 63.4 ± 5.5 μmol·min−1·kg−1, respectively). In particular, PYY3–36 treatment increased glucose uptake in adipose tissue, whereas its impact on glucose disposal in muscle did not attain statistical significance. PYY3–36 treatment shifts the balance of fuel use in favor of fatty acids and enhances insulin sensitivity in mice, where it particularly promotes insulin-mediated glucose disposal. Notably, these metabolic effects of PYY3–36 remain unabated after chronic administration, in contrast to its anorexic effects.

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P007 Eating in alignment with the circadian clock: A strategy to reduce the metabolic impact of nightwork

SLEEP Advances ◽

10.1093/sleepadvances/zpab014.056 ◽

2021 ◽

Vol 2 (Supplement_1) ◽

pp. A23-A24

Author(s):

S Centofanti ◽

L Heilbronn ◽

G Wittert ◽

A Coates ◽

J Dorrian ◽

...

Keyword(s):

Glucose Metabolism ◽

Glucose Tolerance ◽

Mixed Model ◽

Insulin Response ◽

Area Under The Curve ◽

Metabolic Effects ◽

Energy Requirements ◽

Oral Glucose ◽

Recovery Sleep ◽

The Impact

Abstract Nightwork disrupts circadian rhythms and impairs glucose metabolism, increasing the risk for type 2 diabetes. We investigated eliminating or reducing the amount of food consumed during simulated nightwork as a countermeasure to reduce the impact of circadian disruption on glucose metabolism. N=52 healthy, non-shiftworking participants (24.4±4.9 years; 26 Females; BMI 23.8±2.5kg/m2) underwent a 7-day laboratory protocol with an 8h TIB baseline sleep, followed by 4 simulated nightshifts with 7h TIB daytime sleep and an 8h TIB recovery sleep in groups of 4 participants. Each group was randomly assigned to a meal-at-midnight (n=17, 30% energy requirements), snack-at-midnight (n=16, 10% energy requirements) or no-eating-at-midnight (n=19) condition. Total 24h energy and macronutrient intake were constant across conditions. Standard oral glucose tolerance tests (OGTT) were conducted on day2 (baseline), and day7 (recovery). Plasma was sampled at -15, 0, 15, 30, 60, 90, 120, 150 mins, assayed for glucose and insulin. Area under the curve (AUC) was the calculated. Mixed model analyses of glucose AUC found a condition-by-day interaction (p<0.001). Glucose responses to OGTT did not change with nightwork in the no-eating-at-midnight condition (p=0.219) but worsened in the meal-at-midnight (p<0.001) and snack-at-midnight (p=0.022) conditions. Insulin AUC was different by condition (p=0.047). Insulin was highest after nightwork in the no-eating-at-midnight compared to meal-at-midnight (p=0.014) but not snack-at-midnight (p=0.345). Glucose tolerance was impaired by eating-at-midnight, associated with a lower than expected insulin response. Further work is required to determine the effect of meal or snack composition as a strategy to mitigate adverse metabolic effects of nightwork.

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Effects of Metformin and Sitagliptin Monotherapy on Expression of Intestinal and Renal Sweet Taste Receptors and Glucose Transporters in a Rat Model of Type 2 Diabetes

Hormone and Metabolic Research ◽

10.1055/a-1135-9031 ◽

2020 ◽

Vol 52 (05) ◽

pp. 329-335

Author(s):

Minchun Zhang ◽

Rilu Feng ◽

Jiang Yue ◽

Cheng Qian ◽

Mei Yang ◽

...

Keyword(s):

Blood Glucose ◽

Fasting Blood Glucose ◽

Glucose Transporters ◽

Sweet Taste ◽

Glucose Absorption ◽

Taste Receptors ◽

Mrna Levels ◽

Sweet Taste Receptors ◽

Incretin Secretion ◽

Zdf Rats

AbstractDisordered intestinal sweet taste receptors (STRs) are implicated in glucose homeostasis by involving in incretin secretion and glucose absorption. However, the effects of antidiabetic medications on STRs, downstream molecules, and glucose transporters expression are unknown. In our study, ZDF rats (n=24) were randomly treated by metformin (MET, 215.15 mg/kg), sitagliptin (SIT, 10.76 mg/kg), or saline for 4 weeks. Fasting blood glucose and insulin levels were measured, and HOMA-IR and QUICKI index were calculated. One week later, we detected relative mRNA expression of T1R2/T1R3, α-gustducin, TRPM5 and glucose transporters including SGLT1, SGLT2, and GLUT2 in the small intestine and kidney. We found that though both metformin and sitagliptin effectively decreased fasting blood glucose, only metformin improved HOMA-IR and QUICKI (p<0.05). MRNA levels of STRs and sweet taste molecules in duodenum and jejunum were not different among three groups, but those in ileum were dramatically upregulated after SIT (vs. MET p<0.05; vs. CON p<0.01). SGLT1 and GLUT2 in ileum were markedly increased after SIT (p<0.01). In the kidney, expression of SGLT2 and GLUT2 were downregulated in both SIT and MET group (p<0.05). In conclusion, metformin and sitagliptin exerted different effects on expression of STRs and glucose transporters in the gut and kidney. STRs, downstream molecules, and glucose transporters in distal small intestinal were sensitively increased in response to sitagliptin than metformin treatment. Renal glucose transporters were downregulated after metformin and sitagliptin treatment.

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Orosensory Perception of Fat/Sweet Stimuli and Appetite-Regulating Peptides before and after Sleeve Gastrectomy or Gastric Bypass in Adult Women with Obesity

Nutrients ◽

10.3390/nu13030878 ◽

2021 ◽

Vol 13 (3) ◽

pp. 878

Author(s):

Arnaud Bernard ◽

Johanne Le Beyec-Le Bihan ◽

Loredana Radoi ◽

Muriel Coupaye ◽

Ouidad Sami ◽

...

Keyword(s):

Bariatric Surgery ◽

Gastric Bypass ◽

Sleeve Gastrectomy ◽

Gut Hormones ◽

Sweet Taste ◽

Taste Perception ◽

Taste Sensitivity ◽

Adult Women ◽

Before And After ◽

The Impact

The aim of this study was to explore the impact of bariatric surgery on fat and sweet taste perceptions and to determine the possible correlations with gut appetite-regulating peptides and subjective food sensations. Women suffering from severe obesity (BMI > 35 kg/m2) were studied 2 weeks before and 6 months after a vertical sleeve gastrectomy (VSG, n = 32) or a Roux-en-Y gastric bypass (RYGB, n = 12). Linoleic acid (LA) and sucrose perception thresholds were determined using the three-alternative forced-choice procedure, gut hormones were assayed before and after a test meal and subjective changes in oral food sensations were self-reported using a standardized questionnaire. Despite a global positive effect of both surgeries on the reported gustatory sensations, a change in the taste sensitivity was only found after RYGB for LA. However, the fat and sweet taste perceptions were not homogenous between patients who underwent the same surgery procedure, suggesting the existence of two subgroups: patients with and without taste improvement. These gustatory changes were not correlated to the surgery-mediated modifications of the main gut appetite-regulating hormones. Collectively these data highlight the complexity of relationships between bariatric surgery and taste sensitivity and suggest that VSG and RYGB might impact the fatty taste perception differently.

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Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly

Hormone and Metabolic Research ◽

10.1055/a-0594-2404 ◽

2018 ◽

Vol 50 (05) ◽

pp. 408-413 ◽

Cited By ~ 1

Author(s):

Sema Dogansen ◽

Gulsah Yalin ◽

Seher Tanrikulu ◽

Sema Yarman

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Normal Glucose Tolerance ◽

Glucose Metabolism Disorders ◽

Insulin Resistant ◽

Normal Glucose ◽

Resistant Group ◽

The Impact

AbstractIn this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly.

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Binding Properties of a Dinuclear Zinc(II) Salen-Type Molecular Tweezer with a Flexible Spacer in the Formation of Lewis Acid-Base Adducts with Diamines

Inorganics ◽

10.3390/inorganics9060049 ◽

2021 ◽

Vol 9 (6) ◽

pp. 49

Author(s):

Gabriella Munzi ◽

Giuseppe Consiglio ◽

Salvatore Failla ◽

Santo Di Bella

Keyword(s):

Lewis Acid ◽

Degrees Of Freedom ◽

Binding Constants ◽

Molecular Structures ◽

Acid Base ◽

Binding Properties ◽

Binding Characteristics ◽

Fluorescence Studies ◽

Flexible Spacer ◽

Molecular Tweezer

In this paper we report the binding properties, by combined 1H NMR, optical absorption, and fluorescence studies, of a molecular tweezer composed of two Zn(salen)-type Schiff-base units connected by a flexible spacer, towards a series of ditopic diamines having a strong Lewis basicity, with different chain length and rigidity. Except for the 1,2-diaminoethane, in all other cases the formation of stable 1:1 Lewis acid-base adducts with large binding constants is demonstrated. For α,ω-aliphatic diamines, binding constants progressively increase with the increasing length of the alkyl chain, thanks to the flexible nature of the spacer and the parallel decreased conformational strain upon binding. Stable adducts are also found even for short diamines with rigid molecular structures. Given their preorganized structure, these latter species are not subjected to loss of degrees of freedom. The binding characteristics of the tweezer have been exploited for the colorimetric and fluorometric selective and sensitive detection of piperazine.

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Abstract 037: Role of Pro-opiomelanocortin (POMC) Specific PTP1B in Differential Regulation of Blood Pressure, Liver Lipid Accumulation and Glucose Tolerance in Response to a High Fat Diet

Hypertension ◽

10.1161/hyp.68.suppl_1.037 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Nicola Aberdein ◽

Jussara M do Carmo ◽

Zhen Wang ◽

Taolin Fang ◽

Cecilia P de Lara ◽

...

Keyword(s):

Blood Pressure ◽

Glucose Tolerance ◽

Fat Mass ◽

Lipid Accumulation ◽

High Fat Diet ◽

Acute Stress ◽

Liver Lipid ◽

Liver Weight ◽

Metabolic Effects ◽

High Fat

Obese subjects are often resistant to leptin’s metabolic effects although blood pressure (BP) and sympathetic nervous system responses appear to be preserved. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of leptin signaling, may play a role in promoting this selective leptin resistance and causing metabolic dysfunction in obesity. Our previous studies suggest that the chronic BP responses to leptin are mediated via activation of pro-opiomelanocortin (POMC) neurons. The goal of this study was to determine if PTP1B in POMC neurons differentially controls metabolic functions and BP in mice fed a high fat diet (HFD). Male mice with POMC specific PTP1B deletion (POMC/PTP1B -/- ) and littermate controls (PTP1B flox/flox ) were fed a HFD from 6 to 22 wks of age. Baseline BP after 16 weeks of a HFD (95±2 vs. 95±3 mmHg) and BP responses to acute stress (Δ32±0 vs. Δ32±6 mmHg), measured by telemetry, were not different in POMC/PTP1B -/- compared to control mice, respectively. Heart rate (HR) was not different in POMC/PTP1B -/- and control mice during acute stress (699±4 vs. 697±15 bpm, respectively). Total body weight (TBW) and fat mass were reduced at 20 weeks of age in POMC/PTP1B -/- compared to controls (36.7±0.1 vs. 42.0±1 g TBW and 12.7±0.4 vs. 16.1±1.0 g fat mass, respectively). Liver weight of POMC/PTP1B -/- mice was less than in controls, and this was evident even when liver weight was normalized as % of TBW (4.5±0.2 vs. 5.0±0.2 %). POMC/PTP1B -/- males had reduced liver lipid accumulation compared to controls as measured by EchoMRI (0.08±0.03 vs. 0.15±0.03 g/g liver weight). Glucose tolerance was also improved by 46% in POMC/PTP1B -/- compared to controls as measured by AUC, 25856±1683 vs. 47267±5616 mg/dLx120min, respectively. These findings indicate that PTP1B signaling in POMC neurons plays a crucial role in regulating liver lipid accumulation and glucose tolerance but does not appear to mediate changes in BP or BP responses to acute stress in mice fed a high HFD (supported by NHLBI-PO1HL51971 and NIGMS P20GM104357)

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The impact of ageing, fasting and high-fat diet on central and peripheral glucose tolerance and glucose-sensing neural networks in the arcuate nucleus

Journal of Neuroendocrinology ◽

10.1111/jne.12528 ◽

2017 ◽

Vol 29 (10) ◽

pp. e12528 ◽

Cited By ~ 4

Author(s):

M. van den Top ◽

F.-Y. Zhao ◽

R. Viriyapong ◽

N. J. Michael ◽

A. C. Munder ◽

...

Keyword(s):

Neural Networks ◽

Glucose Tolerance ◽

High Fat Diet ◽

Arcuate Nucleus ◽

Glucose Sensing ◽

High Fat ◽

The Impact

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The effect of maternal and post-weaning low and high glycaemic index diets on glucose tolerance, fat deposition and hepatic function in rat offspring

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415007965 ◽

2015 ◽

Vol 7 (3) ◽

pp. 320-329 ◽

Cited By ~ 5

Author(s):

J. Gugusheff ◽

P. Sim ◽

A. Kheng ◽

S. Gentili ◽

M. Al-Nussairawi ◽

...

Keyword(s):

Glucose Tolerance ◽

Later Life ◽

Hepatic Function ◽

Female Offspring ◽

Glycaemic Index ◽

Visceral Adiposity ◽

Beneficial Effects ◽

Pregnancy And Lactation ◽

Total Body ◽

The Impact

Clinical studies have reported beneficial effects of a maternal low glycaemic index (GI) diet on pregnancy and neonatal outcomes, but the impact of the diet on the offspring in later life, and the mechanisms underlying these effects, remain unclear. In this study, Albino Wistar rats were fed either a low GI (n=14) or high GI (n=14) diet during pregnancy and lactation and their offspring weaned onto either the low or high GI diet. Low GI dams had better glucose tolerance (AUC[glucose], 1322±55 v. 1523±72 mmol min/l, P<0.05) and a lower proportion of visceral fat (19.0±2.9 v. 21.7±3.8% of total body fat, P<0.05) compared to high GI dams. Female offspring of low GI dams had lower visceral adiposity (0.45±0.03 v. 0.53±0.03% body weight, P<0.05) and higher glucose tolerance (AUC[glucose], 1243±29 v. 1351±39 mmol min/l, P<0.05) at weaning, as well as lower hepatic PI3K-p85 mRNA at 12 weeks of age. No differences in glucose tolerance or hepatic gene expression were observed in male offspring, but the male low GI offspring did have reduced hepatic lipid content at weaning. These findings suggest that consuming a low GI diet during pregnancy and lactation can improve glucose tolerance and reduce visceral adiposity in the female offspring at weaning, and may potentially produce long-term reductions in the hepatic lipogenic capacity of these offspring.

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