Effects of D-allulose on glucose tolerance and insulin response to a standard oral sucrose load: results of a prospective, randomized, crossover study

IntroductionCurrent dietary guidelines recommend limiting sugar intake for the prevention of diabetes mellitus (DM). Reduction in sugar intake may require sugar substitutes. Among these, D-allulose is a non-calorie rare monosaccharide with 70% sweetness of sucrose, which has shown anti-DM effects in Asian populations. However, there is limited data on the effects of D-allulose in other populations, including Westerners.Research design and methodsThis was a prospective, randomized, double-blind, placebo-controlled, crossover study conducted in 30 subjects without DM. Study participants were given a standard oral (50 g) sucrose load and randomized to placebo or escalating doses of D-allulose (2.5, 5.0, 7.5, 10.0 g). Subjects crossed-over to the alternate study treatment after 7–14 days of wash out. Plasma glucose and insulin levels were measured at five time points: before and at 30, 60, 90 and 120 min after ingestion.ResultsD-allulose was associated with a dose-dependent reduction of plasma glucose at 30 min compared with placebo. In particular, glucose was significantly lower with the 7.5 g (mean difference: 11; 95% CI 3 to 19; p=0.005) and 10 g (mean difference: 12; 95% CI 4 to 20; p=0.002) doses. Although glucose was not reduced at the other time points, there was a dose-dependent reduction in glucose excursion compared with placebo, which was significant with the 10 g dose (p=0.023). Accordingly, at 30 min D-allulose was associated with a trend towards lower insulin levels compared with placebo, which was significant with the 10 g dose (mean difference: 14; 95% CI 4 to 25; p=0.006). D-allulose did not reduce insulin at any other time point, but there was a significant dose-dependent reduction in insulin excursion compared with placebo (p=0.028), which was significant with the 10 g dose (p=0.002).ConclusionsThis is the largest study assessing the effects of D-allulose in Westerners demonstrating an early dose-dependent reduction in plasma glucose and insulin levels as well as decreased postprandial glucose and insulin excursion in subjects without DM. These pilot observations set the basis for large-scale investigations to support the anti-DM effects of D-allulose.Trial registration numberNCT02714413.

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Influence of low- and high-protein diets on glucose homeostasis in the rat

British Journal Of Nutrition ◽

10.1079/bjn19880123 ◽

1988 ◽

Vol 60 (3) ◽

pp. 509-516 ◽

Cited By ~ 16

Author(s):

W. Okitolonda ◽

S. M. Brichard ◽

A. M. Pottier ◽

J. C. Henquin

Keyword(s):

Glucose Homeostasis ◽

Plasma Glucose ◽

Control Diet ◽

Protein Energy Malnutrition ◽

Insulin Response ◽

High Protein Diet ◽

High Protein ◽

Oral Glucose ◽

Insulin Levels ◽

Energy Deprivation

1. The influence of the protein content of the diet on glucose homeostasis was studied in the rat. Rats of 28 d of age received ad lib. a control diet containing (g/kg) 150 protein (P15), or a diet containing 50 protein (P5) or 450 protein (P45). Since P5 rats spontaneously reduced their food intake, a fourth group of rats (P25) received the same amount of energy as P5 rats and the same amount of protein as P15 rats.2. After 12–13 weeks on these diets, plasma glucose and insulin levels were similar in fed P45, P25 and control P15 rats, but were lower in P5 rats. In fasted animals, plasma glucose and insulin levels were also decreased in P5 rats, whereas plasma glucose levels were increased in both P45 and P25 animals.3. During an oral glucose tolerance test, the glucose rise was only slightly larger in P5 than in P15 rats in spite of a considerably smaller increase in insulin levels. P45 rats displayed a normal tolerance to glucose with a normal insulin response, whereas tolerance to glucose was slightly poorer in P25 rats in spite of a normal insulin response.4. Pancreatic insulin stores were lower in P5 than in control P15 rats, not only because of the smaller size of their pancreas, but also because of a decrease in the insulin concentration in the gland. A much smaller decrease was also observed in P25 rats, whereas insulin reserves were not altered in P45 rats.5. It is concluded that the changes in glucose homeostasis observed in protein-energy malnutrition (P5 rats) are due to protein deprivation rather than to energy deprivation. A high-protein diet has little influence on glucose homeostasis in the rat.

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Fasting Plasma Glucose Indicates Reversibility of Acute Insulin Response after Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes of Various Duration

Diabetes ◽

10.2337/db18-999-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 999-P

Author(s):

LIEHUA LIU ◽

SIYUE YANG ◽

JIANBIN LIU ◽

LI HAI ◽

JUAN LIU ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Therapy ◽

Intensive Insulin Therapy ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Insulin Response ◽

Acute Insulin Response ◽

Short Term ◽

Fasting Plasma

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The Insulin Response to the Gut Hormone GIP After Near-normalisation of Plasma Glucose in Patients With Type 2 Diabetes

Case Medical Research ◽

10.31525/ct1-nct04228484 ◽

2020 ◽

Author(s):

Keyword(s):

Type 2 Diabetes ◽

Plasma Glucose ◽

Insulin Response ◽

Gut Hormone

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Insulin secretion and substrate homeostasis in prolonged hypothermia in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.6.r1035 ◽

1988 ◽

Vol 255 (6) ◽

pp. R1035-R1040

Author(s):

R. Hoo-Paris ◽

M. L. Jourdan ◽

L. C. Wang ◽

R. Rajotte

Keyword(s):

Insulin Secretion ◽

Plasma Glucose ◽

Low Temperatures ◽

Plasma Insulin ◽

Glucose Utilization ◽

Exogenous Insulin ◽

Metabolic Substrate ◽

Endogenous Insulin ◽

Dose Dependent Decrease ◽

Dose Dependent

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.

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An engineered IL-2 reprogrammed for anti-tumor therapy using a semi-synthetic organism

Nature Communications ◽

10.1038/s41467-021-24987-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jerod L. Ptacin ◽

Carolina E. Caffaro ◽

Lina Ma ◽

Kristine M. San Jose Gall ◽

Hans R. Aerni ◽

...

Keyword(s):

Nk Cells ◽

Large Scale ◽

Tumor Therapy ◽

Covalent Modification ◽

Synthetic Dna ◽

Expansion Characteristic ◽

Synthetic Organisms ◽

Dose Dependent ◽

Receptor Beta

AbstractThe implementation of applied engineering principles to create synthetic biological systems promises to revolutionize medicine, but application of fundamentally redesigned organisms has thus far not impacted practical drug development. Here we utilize an engineered microbial organism with a six-letter semi-synthetic DNA code to generate a library of site-specific, click chemistry compatible amino acid substitutions in the human cytokine IL-2. Targeted covalent modification of IL-2 variants with PEG polymers and screening identifies compounds with distinct IL-2 receptor specificities and improved pharmacological properties. One variant, termed THOR-707, selectively engages the IL-2 receptor beta/gamma complex without engagement of the IL-2 receptor alpha. In mice, administration of THOR-707 results in large-scale activation and amplification of CD8+ T cells and NK cells, without Treg expansion characteristic of IL-2. In syngeneic B16-F10 tumor-bearing mice, THOR-707 enhances drug accumulation in the tumor tissue, stimulates tumor-infiltrating CD8+ T and NK cells, and leads to a dose-dependent reduction of tumor growth. These results support further characterization of the immune modulatory, anti-tumor properties of THOR-707 and represent a fundamental advance in the application of synthetic biology to medicine, leveraging engineered semi-synthetic organisms as cellular factories to facilitate discovery and production of differentiated classes of chemically modified biologics.

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Insulin and glucagon in rats with Islet cell tumors Induced by small doses of streptozofoclii

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y81-121 ◽

1981 ◽

Vol 59 (8) ◽

pp. 818-823 ◽

Cited By ~ 2

Author(s):

Gen Yoshino ◽

Tsutomu Kazumi ◽

Soichiro Morita ◽

Shighaki Baba

Keyword(s):

Plasma Glucose ◽

Islet Cell ◽

Insulin Response ◽

Oral Glucose ◽

Islet Cell Tumors ◽

Glucose Levels ◽

Tumor Bearing ◽

Small Doses ◽

Wet Weight ◽

Glucose Plasma

Plasma insulin and glucagon responses to oral glucose loading were examined in rats with islet cell tumors induced by a single intravenous injection of streptozotocin (30 or 40 mg/kg body weight). Twenty-four macroscopic and six microscopic tumors occurred in 21 rats. In 15 of 21 tumor-bearing rats, there was exaggerated insulin release in response to oral glucose. Plasma glucose levels did not rise with the oral glucose load and were comparable to those seen in normal animals. Hence these rats are described as having "responsive tumors." In six rats with "nonresponsive tumors" there was no insulin response and the plasma glucose levels rose. No significant differences in plasma glucagon levels were observed between the two groups. Nonresponsive tumors as well as responsive tumors contained a significant amount of extractable insulin (17.68 ± 8.60 and 35.07 ± 10.05 mg/g wet weight, respectively) and detectable amounts of immunoreactive glucagon (1.47 ± 0.61 and 2.24 ± 0.67 μg/g wet weight, respectively).These results suggest that a small dose of streptozotocin produces two types of islet cell tumors. One is insulin producing and insulin secreting whereas the other is insulin producing but not insulin secreting.

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Subcutaneous glucagon-like peptide-1 improves postprandial glycaemic control over a 3-week period in patients with early Type 2 diabetes

Clinical Science ◽

10.1042/cs0950325 ◽

1998 ◽

Vol 95 (3) ◽

pp. 325-329 ◽

Cited By ~ 22

Author(s):

Jeannie F. TODD ◽

C. Mark B. EDWARDS ◽

Mohammad A. GHATEI ◽

Hugh M. MATHER ◽

Stephen R. BLOOM

Keyword(s):

Type 2 Diabetes ◽

Glycaemic Control ◽

Plasma Glucose ◽

Test Meal ◽

Insulin Response ◽

Standard Test ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

First Phase Insulin Response

1.Glucagon-like peptide-1 (7-36) amide (GLP-1) is released into the circulation after meals and is the most potent physiological insulinotropic hormone in man. GLP-1 has the advantages over other therapeutic agents for Type 2 diabetes of also suppressing glucagon secretion and delaying gastric emptying. One of the initial abnormalities of Type 2 diabetes is the loss of the first-phase insulin response, leading to postprandial hyperglycaemia. 2.To investigate the therapeutic potential of GLP-1 in Type 2 diabetes, six patients were entered into a 6-week, double-blind crossover trial during which each received 3 weeks treatment with subcutaneous GLP-1 or saline, self-administered three times a day immediately before meals. A standard test meal was given at the beginning and end of each treatment period. 3.GLP-1 reduced plasma glucose area under the curve (AUC) after the standard test meal by 58% (AUC, 0–240 ;min: GLP-1 start of treatment, 196±141 ;mmol·min-1·l-1; saline start of treatment, 469±124 ;mmol·min-1·l-1; F = 16.4, P< 0.05). The plasma insulin excursions were significantly higher with GLP-1 compared with saline over the initial postprandial 30 ;min, the time period during which the GLP-1 concentration was considerably elevated. The plasma glucagon levels were significantly lower over the 240-min postprandial period with GLP-1 treatment. The beneficial effects of GLP-1 on plasma glucose, insulin and glucagon concentrations were fully maintained for the 3-week treatment period. 4.We have demonstrated a significant improvement in postprandial glycaemic control with subcutaneous GLP-1 treatment. GLP-1 improves glycaemic control partially by restoring the first-phase insulin response and suppressing glucagon and is a potential treatment for Type 2 diabetes.

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Segmentation and Pattern Analyses for Three Meals of Postprandial Plasma Glucose Values and Associated Carbs/Sugar Amounts Using GH-Method: Math-Physical Medicine (No. 326)

10.47363/jcrr/2020(2)118 ◽

2020 ◽

Vol 2 (2) ◽

pp. 1-4

Author(s):

Gerald C Hsu ◽

Keyword(s):

Plasma Glucose ◽

Research Work ◽

Exercise Program ◽

Management Program ◽

Conversion Ratio ◽

Lifestyle Management ◽

Postprandial Plasma Glucose ◽

Sugar Intake ◽

Glucose Levels ◽

Segmentation Analysis

The author describes the results of segmentation and pattern analyses of postprandial plasma glucose levels (PPG) and carbs/sugar intake amount (carbs), which are associated with his three daily meals. In this paper, there are three consistent ranges of low, medium, and high for PPG values and carbs/sugar amounts that are used for each meal but with different units. One of the final objectives for this analysis is to calculate the most reasonable and effective conversion ratio between measured PPG in mg/dL and carbs/sugar intake amount in grams, by discovering how much PPG amount would be generated from 1 gram of carbs/sugar intake. This investigation utilized the PPG data and carbs/sugar amount collected during a period of 2+ years from 5/5/2018 to 9/6/2020 with a breakdown of 855 days, including 2,565 meals, 33,345 glucose data, and 33,345 carbs/sugar data. By using the segmentation analysis of his 33,345 PPG data and 2,565 carbs/sugar data, the author has conducted a pattern recognition and segmentation analysis from his PPG profiles with its associated carbs/sugar intake of his food and meals in the past 855 days. Since 12/8/2015, he ceased taking any diabetes medications. In other words, his diabetes control is 100% dependent on his lifestyle management program with no chemical intervention from any medications. Subsequently, he has maintained a stringent exercise program after each meal; therefore, the development of his simplified PPG prediction model, excluding the exercise factor, can be expressed solely with carbs/sugar intake amount. Predicted PPG = (baseline glucose) + (conversion ratio * carbs/sugar amount) In his research work, he found the reasonable and effective conversion ratio between PPG and carbs that ranges from 1.8 mg/dL per gram to 2.5 mg/dL per gram. This simple equation could assist many type 2 diabetes (T2D) patients in controlling their diabetes via carbs/sugar intake amount. During this particular time period, his PPG control via a stringent lifestyle management without medication is highly successful. His estimated mathematically derived HbA1C values should be between 5.56% to 6.05%, which is a satisfactory HbA1C level for a 73-year-old male with a 25-year history of severe diabetes. It should be mentioned that he had an average daily glucose of 280 mg/dL and HbA1C of 11% in 2010. This segmented pattern analyses based on his PPG data and carbs/sugar intake amount offer a useful tool for analyzing other types of biomarkers in a deeper investigation with a wider entry point of research.

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Rapid translocation of hepatic glucokinase in response to intraduodenal glucose infusion and changes in plasma glucose and insulin in conscious rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00218.2003 ◽

2004 ◽

Vol 286 (4) ◽

pp. G627-G634 ◽

Cited By ~ 51

Author(s):

Chang An Chu ◽

Yuka Fujimoto ◽

Kayano Igawa ◽

Joseph Grimsby ◽

Joseph F. Grippo ◽

...

Keyword(s):

Portal Vein ◽

Plasma Glucose ◽

Regulatory Protein ◽

Glucose Infusion ◽

Insulin Levels ◽

Conscious Rats ◽

Glucose Levels ◽

Glucose Ingestion ◽

Plasma Insulin Levels

The rate of liver glucokinase (GK) translocation from the nucleus to the cytoplasm in response to intraduodenal glucose infusion and the effect of physiological rises of plasma glucose and/or insulin on GK translocation were examined in 6-h-fasted conscious rats. Intraduodenal glucose infusion (28 mg·kg-1·min-1 after a priming dose at 500 mg/kg) elevated blood glucose levels (mg/dl) in the artery and portal vein from 90 ± 3 and 87 ± 3 to 154 ± 4 and 185 ± 4, respectively, at 10 min. At 120 min, the levels had decreased to 133 ± 6 and 156 ± 5, respectively. Plasma insulin levels (ng/ml) in the artery and the portal vein rose from 0.7 ± 0.1 and 1.8 ± 0.3 to 11.8 ± 1.5 and 20.2 ± 2.0 at 10 min, respectively, and 12.4 ± 3.1 and 18.0 ± 4.8 at 30 min, respectively. GK was rapidly exported from the nucleus as determined by measuring the ratio of the nuclear to the cytoplasmic immunofluorescence (N/C) of GK (2.9 ± 0.3 at 0 min to 1.7 ± 0.2 at 10 min, 1.5 ± 0.1 at 20 min, 1.3 ± 0.1 at 30 min, and 1.3 ± 0.1 at 120 min). When plasma glucose (arterial; mg/dl) and insulin (arterial; ng/ml) levels were clamped for 30 min at 93 ± 7 and 0.7 ± 0.1, 81 ± 5 and 8.9 ± 1.3, 175 ± 5 and 0.7 ± 0.1, or 162 ± 5 and 9.2 ± 1.5, the N/C of GK was 3.0 ± 0.5, 1.8 ± 0.1, 1.5 ± 0.1, and 1.2 ± 0.1, respectively. The N/C of GK regulatory protein (GKRP) did not change in response to the intraduodenal glucose infusion or the rise in plasma glucose and/or insulin levels. The results suggest that GK but not GKRP translocates rapidly in a manner that corresponds with changes in the hepatic glucose balance in response to glucose ingestion in vivo. Additionally, the translocation of GK is induced by the postprandial rise in plasma glucose and insulin.

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