Acute high-intensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycaemia in patients with type 2 diabetes

High-volume endurance exercise (END) improves glycaemic control in type 2 diabetes (T2D) but many individuals cite 'lack of time' as a barrier to regular participation. High-intensity interval training (HIT) is a time-efficient method to induce physiological adaptations similar to END, but little is known regarding the effect of HIT in T2D. Using continuous glucose monitoring (CGM), we examined the 24-h blood glucose response to one session of HIT consisting of 10 × 60 s cycling efforts at ~90% maximal heart rate, interspersed with 60 s rest. Seven adults with T2D underwent CGM for 24-h on two occasions under standard dietary conditions: following acute HIT and on a non-exercise control day (CTL). HIT reduced hyperglycaemia measured as proportion of time spent above 10 mmol/l (HIT: 4.5 ± 4.4 vs. CTL: 15.2 ± 12.3%, p = 0.04). Postprandial hyperglycaemia, measured as the sum of post-meal areas under the glucose curve, was also lower after HIT vs. CTL (728 ± 331 vs. 1142 ± 556 mmol/l·9 h, p = 0.01). These findings highlight the potential for HIT to improve glycaemic control in T2D.     

Relative and absolute contributions of postprandial and fasting plasma glucose to daytime hyperglycaemia and HbA1c in subjects with Type 2 diabetes

Aims To determine the relative and absolute contributions of postprandial glucose (PPG) and fasting or preprandial plasma glucose (FPG) to daytime hyperglycaemia and HbA_1c respectively, in persons with type 2 diabetes (T2DM). Methods Subjects (n = 52; 37men) had 12hr plasma glucose (PG) profiles determined in response to three serial identical test meals. PPG exposure was calculated for each meal. Excess hyperglycaemia was calculated above a PG concentration of 5.5mmol/l. Fasting hyperglycaemia was the difference between excess hyperglycaemia and PPG exposure. Subjects were divided into three groups according to HbA_1c‐(Gp1:<7.3%;Gp2:7.3%‐8.0%;Gp3:>8.0%) and the relative contribution of PPG exposure and fasting hyperglycaemia to excess hyperglycaemia calculated for each meal. The absolute contribution of PPG and fasting hyperglycaemia to excess HbA_1c (mean HbA_1c–5.1%) was also calculated. Results The relative contributions of PPG exposure to excess hyperglycaemia for the three groups were: 58.3%, 54.3% and 35.4% (P = 0.483—Group 1 vs. Group 2; P = 0.002—Group 2 vs. Group 3) for meal 1; 69.8%, 54.7% and 23.7% (P = 0.163—Group 1 vs. Group 2; P = 0.005—Group 2 vs. Group 3) for meal 2; 85.8%, 70.2% and 48.6% (P = 0.153—Group 1 vs. Group 2; P = 0.046—Group 2 vs. Group 3) for meal 3. Absolute contributions of PPG to excess HbA_1c in the three groups were 1.4%, 1.6% and 1.3% (P = NS). Conclusion The relative contribution of postprandial glucose to excess hyperglycaemia decreases as glycaemic control deteriorates, being dominant with HbA_1c≤ 7.3%, irrespective of the timing of the meal during the day. However, the absolute contribution of postprandial glucose to excess HbA_1c does not differ significantly (～1.5%) with varying glycaemic control.     

Fermented mushroom milk-supplemented dietary fibre prevents the onset of obesity and hypertriglyceridaemia in Otsuka Long-Evans Tokushima fatty rats

AIM: Fermented milk product containing edible mushroom water extracts (mushroom yogurt; MY) has been reported to have glycaemic control and triglyceride-lowering effects in streptozotocin (STZ)-induced diabetic rats and Zucker diabetic fatty (ZDF) rats. Here, we investigated how MY-supplemented dietary fibre (10 and 20%, v/w) influences the onset of obesity and hypertriglyceridaemia in Otsuka Long-Evans Tokushima fatty (OLETF) rats. METHODS: The OLETF rats were fed a powdered chow diet supplemented with MY at the levels of 10 (v/w) and 20% for 6 weeks from 10 weeks of age, but the OLETF control rats were not supplemented. Their weight, fat distribution and lipid profile have been determined. RESULTS: The body weights in MY-fed rats were reduced compared with the control rats. The perirenal fat was decreased in both MY groups, but the visceral and epididymal fats reduced only in the MY 20% group. The concentrations of serum triglyceride and non-esterified fatty acid in MY-fed rats were decreased in a dose-dependent manner. However, the levels of other serum lipid profiles [total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol] were comparable among all rats. CONCLUSION: Anti-obesity and triglyceride lowering by MY-supplemented dietary fibre in OLETF rats might have resulted from the synergistic effect of components in the fermented mushroom-milk product.     

Cilnidipine Improves Insulin Sensitivity in the Otsuka Long-Evans Tokushima Fatty Rat, a Model of Spontaneous NIDDM

Summary. Among the antihypertensive drugs, fast-acting Ca²⁺ antagonists have been reported to worsen insulin sensitivity. This effect may be attributable to reflex increases in sympathetic activity. On the other hand, however, it has been reported that long-acting, dihydropiridine Ca²⁺ antagonists improve insulin-resistance. The purpose of this study was to investigate whether cilnidipine, another long-acting dihydropidine Ca²⁺ antagonist, improves insulin sensitivity in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. 25 weeks OLETF rats were divided into the following groups; normal-diet group, cilnidipine-supplemented group (cilnidipine 3mg/kg/day) and angiotensin II receptor antagonist CS-866-supplemented group (CS-866 1mg/kg/day). As a non-diabetic control, we used Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Glucose infusion rate (GIR), an index of insulin resistance, as measured by the hyperinsulinemic euglycemic clamp technique was significantly decreased in OLETF rats. Cilnidipine-treatment partially but significantly improved insulin sensitivity in addition to systolic blood pressure in OLETF rats at 30 weeks of age, although it did not decrease accumulation of abdominal fat or serum levels of glucose or insulin. CS-866, an angiotensin 2 receptor antagonist, which lowers blood pressure through a different mechanism, did not improve insulin resistant states in OLETF rats. These results suggest that cilnidipine has a beneficial effect on insulin-resistance together with the antihypertensive effect.     

Guar attenuates fall in postprandial blood pressure and slows gastric emptying of oral glucose in type 2 diabetes

Postprandial hypotension occurs frequently in diabetes; the fall in blood pressure is greatest after ingestion of carbohydrate, particularly glucose and, in type 2 diabetes, is related to the rate of gastric emptying. The aim of this study was to determine whether slowing of gastric emptying by guar gum reduces the fall in blood pressure after oral glucose in patients with type 2 diabetes. Eleven type 2 patients managed by diet alone, age 61.9 ± 1.3 years, had measurements of gastric emptying, blood pressure, blood glucose, and serum insulin on two occasions after ingestion of 300 ml water containing 50 g glucose, with or without 9 g guar gum. The magnitude of the fall in blood pressure was less (P < 0.05) and gastric emptying slower (P < 0.05) after guar. Blood glucose (P < 0.05) and serum insulin (P < 0.01) concentrations were lower after guar. The magnitude of the fall in systolic blood pressure was related to gastric emptying of glucose at 30 min on the control day (r = 0.67, P < 0.05). We conclude that guar gum attenuates the fall in blood pressure after oral glucose in patients with type 2 diabetes mellitus, presumably by slowing glucose absorption.     

Metformin reduces the rate of small intestinal glucose absorption in type 2 diabetes

In rodents, metformin slows intestinal glucose absorption, potentially increasing exposure of the distal gut to glucose to enhance postprandial glucagon‐like peptide‐1 (GLP‐1) secretion. We evaluated the effects of metformin on serum 3‐O‐methylglucose (3‐OMG; a marker of glucose absorption) and plasma total GLP‐1 concentrations during a standardized intraduodenal infusion of glucose and 3‐OMG in patients with type 2 diabetes. A total of 12 patients, treated with metformin 850 mg twice daily or placebo for 7 days each in a double‐blind, randomized, crossover design (14 days’ washout between treatments), were evaluated on days 5 or 8 of each treatment (6 subjects each). On each study day, 30 minutes after ingesting 850 mg metformin or placebo, patients received an infusion of glucose (60 g + 5 g 3‐OMG, dissolved in water to 240 mL) via an intraduodenal catheter over the course of 120 minutes. Compared with placebo, metformin was associated with lower serum 3‐OMG ( P < .001) and higher plasma total GLP‐1 ( P = .003) concentrations. The increment in plasma GLP‐1 after metformin vs placebo was related to the reduction in serum 3‐OMG concentrations ( P = .019). Accordingly, metformin inhibits small intestinal glucose absorption, which may contribute to augmented GLP‐1 secretion in type 2 diabetes.     

Contribution of basal and postprandial hyperglycaemia in type 2 diabetes patients treated by an intensified insulin regimen: Impact of pump therapy in the OPT2mise trial

Aims

The relative contribution of basal hyperglycaemia (BHG) and postprandial hyperglycaemia (PPHG) in type 2 diabetes patients treated with multiple daily injections (MDI) of insulin is poorly documented. In this study, the BHG and PPHG of patients from the OPT2mise study who were initially treated with MDI were assessed before randomization and again after 6 months of continuous subcutaneous insulin infusion (CSII).

Materials and Methods

Blinded continuous glucose monitoring (CGM) data were collected in 259 MDI patients after completion of an 8‐week run‐in period. The hyperglycaemic area under the curve (AUC) during the 24‐hour basal period (AUC‐B) and the postprandial period (AUC‐P) were compared with analysis of variance based on contribution to total hyperglycaemia in HbA1c groups (Group 1, <8%; Group 2, 8%‐8.4%; Group 3, 8.5%‐8.9%; Group 4, 9%‐9.4%; Group 5, ≥9.5%). Changes in AUC‐B and AUC‐P were assessed after 6 months of pump therapy in 131 randomized participants with available CGM recordings.

Results

In patients undergoing MDI therapy, AUC‐B was 21.6% to 54.8% lower in Group 4 to 1 (P = .0138 and P = .0002, respectively) in comparison to Group 5. In contrast, AUC‐P did not differ among HbA1c groups (P = .1009). HbA1c correlated with AUC‐B, but not with AUC‐P. After switching to CSII, AUC‐B and AUC‐P decreased by 21% and 17%, respectively. When comparing responders with non‐responders to CSII therapy, no between‐group differences were observed in AUC‐B and AUC‐P.

Conclusions

Basal hyperglycaemia is the major determinant of overall exposure to hyperglycaemia in type 2 diabetes with MDI failure.     

Interindividual and intraindividual variations in postprandial glycemia peak time complicate precise recommendations for self-monitoring of glucose in persons with type 1 diabetes mellitus

Background

In glycemic control, postprandial glycemia may be important to monitor and optimize as it reveals glycemic control quality, and postprandial hyperglycemia partly predicts late diabetic complications. Self-monitoring of blood glucose (SMBG) may be an appropriate technology to use, but recommendations on measurement time are crucial.

Method

We retrospectively analyzed interindividual and intraindividual variations in postprandial glycemic peak time. Continuous glucose monitoring (CGM) and carbohydrate intake were collected in 22 patients with type 1 diabetes mellitus. Meals were identified from carbohydrate intake data. For each meal, peak time was identified as time from meal to CGM zenith within 40–150 min after meal start. Interindividual (one-way Anova) and intraindividual (intraclass correlation coefficient) variation was calculated.

Results

Nineteen patients were included with sufficient meal data quality. Mean peak time was 87 ± 29 min. Mean peak time differed significantly between patients (p = 0.02). Intraclass correlation coefficient was 0.29.

Conclusions

Significant interindividual and intraindividual variations exist in postprandial glycemia peak time, thus hindering simple and general advice regarding postprandial SMBG for detection of maximum values.     

Inhibition of intestinal absorption and improvement of oral glucose tolerance by biguanides in the normal and in the streptozotocin-diabetic rat

Summary In the rat the assumption of a primary effect of moderate doses of biguanides on intestinal absorption is supported by the following results: 1. The tolerance to parenteral glucose administration was not improved. — 2. Afteroral pretreatment the hyperglycaemia induced byoral glucose was decreased. — 3. After pretreatmentin vivo the transport of glucose through the intestinal wall was inhibited. — 4. The intestinal glucose transport was inhibited alsoin vitro in the presence of biguanides at concentrations to be expected in intestinal tissuein vivo after efficient doses. — 5. In the streptozoocin-diabetic rat there was a strong correlation between the feeding state and the hypoglycaemie effect of biguanides. In streptozotocin-diabetic rats previously starved and then refed, the hypoglycaemie effect decreased with decreasing doses of the diabetogenic agent. — 6. The relative potency of various biguanides was similar with regard to their effects on hyperglycaemia and on the intestinal glucose transport. — The results suggest, however, that in the rat further events, probably triggered by the inhibition of intestinal absorption, are involved in the mechanism of action of biguanides.

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Hemmung der intestinalen Glucoseresorption und Verbesserung der oralen Glucosetoleranz durch Biguanide bei normalen und Streptozotocin-diabetischen Ratten

Zusammenfassung Folgende Befunde lassen darauf schließen, daß Biguanide in mäßiger Dosierung bei der Ratte primär die intestinale Absorption beeinflussen: 1. Die parenterale Glucosetoleranz wurde nicht verbessert. — 2. Nachoraler Vorbehandlung wurde die durchorale Glucosegabe induzierte Hyperglykämie vermindert. — 3. NachIn-vivo-Vorbehandlung war der Glucosetransport durch die Darmwand gehemmt. — 4. Der intestinale Glucosetransport wurde auchin vitro in Gegenwart von Biguanid-Konzentrationen gehemmt, die man im intestinalen Gewebe nach Applikation wirksamer Dosen erwarten kann. — 5. In der Streptozotocin-diabetischen Ratte bestand eine strenge Korrelation zwischen Fütterungszust and und hypoglykämischem Effekt. In wiedergefütterten Streptozotocin-Ratten nahm die hypoglykämische Wirkung mit abnehmenden Dosen des diabetogenen Agens ab. — 6. Die relative Wirkungsstärke verschiedener Biguanide bezüglich Verminderung der Hyperglykämie und Hemmung der intestinalen Glucoseaufnahme war vergleichbar. — Die erhobenen Befunde deuten jedoch darauf hin, daß in der Ratte zusätzliche Vorgänge, die möglicherweise durch die Absorptionshemmung ausgelöst werden, am Wirkungsmechanismus der Biguanide wesentlich beteiligt sind.

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Inhibition de l'absorption intestinale et amélioration de la tolérance orale au glucose avec des biguanides chez le rat normal et chez le rat rendu diabétique par le streptozotocine

Résumé Les constatations suivantes permettent la conclusion que l'application de faibles doses de biguanides influence chez le rat premièrement l'absorption intestinale: 1. Aucune amélioration de la tolérance parentérale au glucose. 2. Après un prétraitementoral l'hyperglycémie induite par l'administrationorale de glucose est diminuée. — 3. Après un prétraitementin vivo le transport de glucose par la paroi intestinale est freiné. — 4. Des concentrations de biguanides que l'on pourrait rencontrerin vivo dans le tissu intestinal (après traitement avec des dosages efficaces) provoque également une inhibition du transport de glucose dans l'intestinin vitro. — 5. Chez le rat rendu diabétique par streptozotocine il existe une forte corrélation entre l'alimentation et l'effet hypoglycémique. Chez le rat réalimenté l'effet hypoglycémique diminue après l'administration de doses décroissantes de l'agent diabétogène. — 6. La puissance relative de divers biguanides par rapport à la diminution de l'hypoglycémie et l'inhibition du transport intestinal de glucose peut être comparée. — Les résultats trouvés chez le rat font cependant allusion au fait que l'inhibition de l'absorption intestinale n'est pas la seule action des biguanides. Il semble qu'il y a encore d'autres facteurs reliés à cette inhibition.

     

What is the relative contribution of blood glucose levels at different time points of the day to HbA1c in Type 1 diabetes?

AIMS: To evaluate the relative contribution of blood glucose levels at different time points of the day to HbA(1c) in Type 1 diabetes. METHODS: Consecutive home blood glucose records (n = 146) from 71 Type 1 diabetic patients who were on an intensive diabetes therapy programme were examined. Each home blood glucose record included six daily blood glucose profiles over 2 months. The relationship between glycaemic values at each time point and HbA(1c) measured at the end of each record period was analysed. RESULTS: Significant linear correlations were found between HbA(1c) and glycaemia at each time point of the day (ranged from 0.413 to 0.593), the strongest being with predinner glycaemia (r = 0.593; P = 0.000). Total daily glycaemia, mean preprandial and mean postprandial glycaemia were also significant and linearly correlated with HbA(1c) (r = 0.701; r = 0.686; r = 0.620, respectively; P < 0.0001). Multiple linear regression analysis showed that predinner, prebreakfast and post-breakfast glycaemia correlated significantly and independently with HbA(1c). The model accounted for 47.8% of the variance in HbA(1c). CONCLUSIONS: Our study shows that among individual time points, prebreakfast and predinner are those with more influence on HbA(1c) in Type 1 diabetes and, to a lesser extent, post breakfast. It also confirms that preprandial glycaemia better predicts overall glycaemic control in Type 1 diabetes than postprandial glycaemia.     

Effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects

AIM: To identify the effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) in single administration on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects. METHODS: A randomized, single-blind, cross-over, clinical trial was carried out in 14 young, healthy, non-obese, volunteers. A basal metabolic profile, which included glucose level, insulin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinine, and uric acid, was measured. Subjects received a single administration of 300 kcal, gauged with water at 350 ml, of each of the following (at least 3 days apart): glucose 75 g, polymeric supplement (Ensure high calcium) 315 ml or Glucerna SR 323 ml. At the beginning of each administration and 30, 60, 90 and 120 min later, glucose and insulin concentrations were measured. Areas under the curve of glucose and insulin were calculated. First-phase and total insulin secretions and insulin sensitivity were also estimated. RESULTS: Glucose level at 120 min was significantly lower after receiving Ensure high calcium or Glucerna SR. Administration of Glucerna SR resulted in a significant reduction in the areas under the curve of glucose and insulin, as well as in total insulin secretion with a tendency to be lower in their first phase. Insulin sensitivity was increased. CONCLUSIONS: A single administration of Glucerna SR to healthy subjects decreased the postprandial glucose and insulin states, as well as the insulin secretion; insulin sensitivity increased.     

Relative contribution of glycogenolysis and gluconeogenesis to hepatic glucose production in control and diabetic rats. A re-examination in the presence of euglycaemia

Summary Several studies have suggested that, in non-insulin-dependent diabetes mellitus, augmented gluconeogenesis is responsible for increased endogenous glucose production (EGP) and in the end determines fasting hyperglycaemia. However, human and animal studies have been conducted by comparing euglycaemic control subjects to hyperglycaemic diabetic probands. We measured EGP and hepatic gluconeogenesis comparing control and diabetic rats in the fasting state (with diabetic animals in hyperglycaemia), re-examining them in the presence of identical euglycaemia (with diabetic rats made acutely euglycaemic through i. v. phloridzin) or during a hyperinsulinaemic clamp. All rats were infused with [3-³H]-glucose and [U-¹⁴C]-lactate; the ratio between ¹⁴C-uridine-diphosphoglucose (reflecting ¹⁴C-glucose 6-phosphate) and 2 ·¹⁴C-phosphoenolpyruvate specific activities (both purified by high performance liquid chromatography from liver) measured hepatic gluconeogenesis. In diabetic animals, although overall EGP ( ∼ 19.5 mg · kg^–1· min^–1) remained unaffected by experimental euglycaemia, the contribution of glycogenolysis largely increased (from 5.4 to 11.7 mg · kg^–1· min^–1, hyper- vs euglycaemia) while gluconeogenesis decreased (from 14.0 to 8.1 mg · kg^–1? min^–1); both were responsible for the augmented EGP (control rats, EGP: 12.7 mg · kg^–1· min^–1; gluconeogenesis: 5.9 mg · kg^–1· min^–1; glycogenolysis: 6.7 mg · kg^–1· min^–1). Finally, during insulin clamp, gluconeogenesis and glycogenolysis were similarly decreased, and both contributed to the hepatic insulin-resistance of diabetic animals. We conclude that, in this model of non-insulin-dependent diabetes, augmented gluconeogenesis is not primarily responsible for fasting hyperglycaemia and hepatic insulin resistance. Finally, failure to accurately match the experimental conditions in which diabetic and control humans or animals are compared affects gluconeogenesis, overestimating its role in determining hyperglycaemia. [Diabetologia (1998) 41: 307–314] Received: 10 September 1997 and in revised form: 13 November 1997     

The effects of hyperglycaemia on isotopic measurement of glucose utilisation using [23H], [33H] and [614C] glucose in patients with Type 1 (insulin-dependent) diabetes mellitus

Summary To determine whether hyperglycaemia alters the accuracy with which [2³H] and [3³H]glucose reflect glucose turnover measured with [6¹⁴C]glucose in patients with Type 1 (insulin-dependent) diabetes mellitus, glucose utilisation rates were measured during a simultaneous infusion of [2³H], [3³H] and [6¹⁴C]glucose after maintenance of normoglycaemia overnight and when glucose concentrations were clamped at 5.3, 7.5 and 9.7 mmol/l while insulin and glucagon concentrations were held constant. Glucose utilisation rates determined with all three isotopes were comparable in the diabetic patients at all glucose concentrations studied. On the other hand, glucose utilisation rates in nondiabetic subjects determined with [6¹⁴C]glucose were greater (p<0.01) than those determined with [3³H]glucose and lower (p<0.04) than those determined with [2³H]glucose during the 5.3, 7.5 and 9.7 mmol/l clamps. Nevertheless, glucose utilisation rates in the diabetic patients were lower (p<0.05) than those in the nondiabetic subjects for each glucose isotope. We conclude that hyperglycaemia does not alter the pattern of metabolism of [2³H] or [3³H]glucose in patients with Type 1 (insulin-dependent) diabetes mellitus.     

On the origin of hyperglycaemia in the obese-hyperglycaemic mouse (obob): Effect of diet on blood glucose and serum insulin inobob and gold-thioglucose obese mice

Summary Obese-hyperglycaemic mice (obob), goldthioglucose obese (GTG-obese) and normal control mice were fed a high-carbohydrate and a carbohydrate-free diet. Blood glucose and serum insulin levels were influenced by the diet in all animals studied, but more so in theobob and GTG-obese. Blood glucose levels were equally raised in both types of obesity. Serum insulin of GTG-obese showed a marked elevation above normal but failed to reach the serum insulin levels of theobob. The blood glucose ofobob and lean controls remained constant when fed the carbohydrate-free diet. Under these conditions, a trace amount of U-¹⁴C-glucose was injected intravenously. The rate of¹⁴C-glucose disappearance from the blood followed first-order kinetics and did not differ betweenobob and lean mice, suggesting a similar fractional rate of glucose uptake by tissues. The presence of a normal fractional rate of glucose extraction by the tissues ofobob, together with their hyperglycaemia and a normal volume of glucose distribution suggests an increased absolute rate of tissue glucose uptake. This increase is likely to be due to the expanded mass of adipose tissue in these animals.

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Über die Ursache der Hyperglykämie bei der fettsüc-htighyperglykämischen Maus (obob): Einwirkung der Diät auf die Blutglucose und das Serum Insulin bei obob und fettsüchtigem Goldthioglucosemäusen

Zusammenfassung Fettsüchtig-hyperglykämische (obob), fettsüchtige Goldthioglucose-(GTG-obese) und normale Kontrollmäuse erhielten einmal eine Diät mit hohem Kohlenhydratgehalt und zum anderen eine kohlenhydratfreie Diät. Bei allen Tieren wurde die Blutglucose und der Blutinsulinspiegel durch die Diät beeinflußt, am meisten aber bei den obob und GTG-obese Mäusen. Der Blutzuckerspiegel erhöhte sich bei beiden Fettsuchtstypen in gleichem Maße. Die Insulinspiegel der GTG-Mäuse waren erhöht, erreichten aber nicht die Werte der obob-Mäuse. Während der Verabreichung der kohlenhydratfreien Diät blieben die Blutzuckerspiegel der obob- und der Kontrollmäuse konstant. Unter diesen Versuchsbedingungen wurde eine Spürdosis von¹⁴C-Glucose i.v. injiziert. Die Abbaurate der Blut-¹⁴C-Glucose folgte einer Kinetik erster Ordnung und wies keinen Unterschied zwischen obob- und Kontrollmäusen auf, was auf eine ähnliche fraktionierte Aufnahmerate der Glucose durch das Gewebe schließen läßt. Das Vorhandensein einer normalen fraktionierten Rate der Glucoseextraktion durch die Gewebe bei obob-Mäusen läßt im Zusammenhang mit der Hyperglykämie und einem normalen Verteilungsvolumen für Glucose eine erhöhte absolute Rate der Glucoseaufnahme durch die Gewebe vermuten. Die Erhöhung ist wahrscheinlich auf die große Fettmasse dieser Tiere zurückzuführen.

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L'origine de l'hyperglycemie chez la souris obèse-hyperglycémique (obob): Effet du régime sur le niveau de la glycémie et de l'insuline du sérum chez obob et chez la souris rendue obèse par aurothioglucose

Résumé Un régime riche ou dépourvu d'hydrates de carbone a été donné à un groupe de souris obèse-hyperglycémique (obob), à un deuxième groupe de souris rendues obèses par aurothioglucose (GTG-obèse) et à un groupe de témoins. La glycémie et l'insulinémie ont été modifiées par le régime chez tous les animaux et particulièrement chez lesobob etGTG-obèses. Le niveau de la glycémie était élevé de façon égale chez les deux groupes de souris obèses. L'insulinémie des souris GTG-obèses était considérablement augmentée mais n'atteignait pas le niveau de l'insulinémie observée chez lesobob. Le taux de glycémie desobob et des témoins est demeuré constant quand les animaux recevaient le régime dépourvu d'hydrates de carbone. A ce stade, nous avons injecté par voie intraveineuse une quantité traceuse de U-¹⁴C-glucose. La vitesse de disparition du traceur obéissait à une cinétique d'ordre un et était semblable chez lesobob et les témoins, suggérant ainsi que l'utilisation fractionnelle du glucose était semblable chez les deux groupes. L'existence d'une utilisation fractionelle normale du glucose chez lesobob jointe à l'hyperglycémie et à un volume normal de distribution du glucose suggère que l'utilisation absolue du glucose chez ces animaux est augmentée. Cette augmentation est vraisemblablement due à l'expansion du tissu adipeux chez lesobob.

     

Haem in the gut. I. Fate of haemoproteins and the absorption of haem

Haem (FeII-protoporphyrin-IX) is presented to the gut lumen as haemoproteins derived from exogenous dietary) and endogenous (mucosal cell desquamation and bleeding) sources. Haemoproteins such as haemoglobin, myoglobin and catalase undergo hydrolysis by luminal proteases to release the haem. Released haem is maintained in a soluble form in the gut lumen by the products of haemoprotein digestion. Chelators of elemental iron do not bind haem-iron and so haem-iron is better absorbed than elemental iron. Haem-iron does not exchange with luminal elemental iron. Mucosal uptake of haem is limited. Less than 10% binds to the brush border of the villus cell. Although the mechanisms by which haem binds to the brush border and is transported to the intracellular environment are poorly understood, it is known that some haem is transferred to secondary lysosomes where the porphyrin ring is split to release iron and form bilirubin. Depending upon the composition of the diet, the iron released from haem within the villus cell can be the major physiological source of iron. In iron-deficiency in humans, absorption of haem-iron can increase threefold whereas absorption of elemental-iron can increase tenfold. These observations indicate that haem-iron and elemental-iron are absorbed via different mechanisms which are subject to different regulation. For haem-iron to be absorbed, the haem itself must be taken up by the mucosa.