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Biomedical subjects

M Stumvoll

Publications and source records attributed to M Stumvoll.

At least 109 records · Page 6Linked to original sources
PubMed1997

Renal glucose production and utilization: new aspects in humans.

According to current textbook wisdom the liver is the exclusive site of glucose production in humans in the postabsorptive state. Although many animal and in vitro data have documented that the kidney is capable of gluconeogenesis, production of glucose by the human kidney in the postabsorptive state has generally been regarded as negligible. This traditional view is based on net balance measurements which, other than after a prolonged fast or during metabolic acidosis, showed no significant net renal glucose release. However, recent studies have refuted this view by combining isotopic and balance techniques, which have demonstrated that renal glucose production accounts for 25% of systemic glucose production. Moreover, these studies indicate that glucose production by the human kidney is stimulated by epinephrine, inhibited by insulin and is excessive in diabetes mellitus. Since renal glucose release is largely, if not exclusively, due to gluconeogenesis, it is likely that the kidney is as important a gluconeogenic organ as the liver. The most important renal gluconeogenic precursors appear to be lactate, glutamine and glycerol. The implications of these recent findings on the understanding of the physiology and pathophysiology of human glucose metabolism are discussed.

Animals↗
PubMed1997

Regulation of gluconeogenesis by glutamine in normal postabsorptive humans.

There is evidence that glutamine may act as a regulator of protein, free fatty acid, and glycogen metabolism. To test the hypothesis that glutamine may act as a physiological regulator of gluconeogenesis, we infused 16 normal postabsorptive volunteers with glutamine at a rate (11.4 micromol kg(-1) x min(-1)) estimated to approximate its appearance in plasma after a protein meal and assessed changes in production of glucose from glutamine, systemic glucose appearance and disposal, and uptake and release of glucose, glutamine, and alanine by forearm skeletal muscle. Although infusion of glutamine increased plasma glutamine concentration and turnover only threefold (from 0.63 +/- 0.03 to 1.95 +/- 0.10 mmol/l and from 5.43 +/- 0.24 to 14.85 +/- 0.66 micromol x kg(-1) x min(-1), respectively; P < 0.001), formation of glucose from glutamine increased sevenfold from 0.55 +/- 0.03 to 3.74 +/- 0.28 micromol x kg(-1) x min(-1) (P < 0.001). Formation of glucose from alanine was also stimulated (0.52 +/- 0.05 vs. 0.75 +/- 0.04 micromol x kg(-1) x min(-1); P < 0.001) in the absence of a change in plasma alanine concentration. Furthermore, glutamine infusion decreased its own de novo synthesis (4.55 +/- 0.22 vs. 2.81 +/- 0.62 micromol x kg(-1) x min(-1);P < 0.02) while increasing that of alanine (2.82 +/- 0.32 vs. 3.56 +/- 0.32 micromol x kg(-1) x min(-1); P < 0.002). Systemic glucose appearance, systemic glucose disposal, and forearm balance of glucose and alanine were not altered. Because the stimulatory effects of glutamine on gluconeogenesis occurred in the absence of changes in plasma insulin and glucagon levels, these results provide evidence that, in humans, glutamine may act both as a substrate and as a regulator of gluconeogenesis as well as a modulator of its own metabolism.

Alanine↗
PubMed1997

Steady-state and non-steady-state measurements of plasma glutamine turnover in humans.

To compare steady-state glutamine turnover using nitrogen, carbon, and hydrogen tracers and to test the validity of monocompartmental equations to determine plasma glutamine turnover under non-steady-state conditions, we infused 10 normal postabsorptive volunteers simultaneously with [3,4-3H]glutamine, [2-15N]glutamine, and [U-14C]glutamine for 4 h to isotopic steady state. Eight of the ten subjects were subsequently infused in a stepwise fashion with exogenous glutamine. Plasma glutamine enrichment and specific activities fit a monoexponential model well (r = 0.89, 0.92, and 0.92 for [2-15N]-, [U-14C]-, and [3,4-3H]glutamine, respectively). Volumes of distribution for each tracer (362 +/- 58, 433 +/- 51, and 446 +/- 63 ml/kg) and the transfer rate constants (0.0224 +/- 0.0020, 0.0222 +/- 0.0020, and 0.0240 +/- 0.0023 min(-1)) for [2-15N]-, [U-14C]-, and [3,4-3H]glutamine, respectively, were not significantly different from one another. However, turnover of glutamine determined with [3,4-3H]glutamine (6.14 +/- 0.54 micromol x kg(-1) x min(-1)) exceeded that determined with [U-14C]glutamine (5.72 +/- 0.541 micromol x kg(-1) x min(-1); P < 0.03), which in turn exceeded that determined with [2-15N]glutamine (4.67 +/- 0.39 micromol x kg(-1) x min(-1), P < 0.01). The monocompartmental non-steady-state equations of both DeBodo et al. (DeBodo, R., R. Steele, A. Dunn, and J. Bishop. Rec. Prog. Horm. Res. 19: 445-448, 1963) and Finegood et al. (Finegood, D., R. Bergman, and M. Vranic. Diabetes 36: 914-924, 1987) yielded acceptable approximations of predicted rates of glutamine plasma appearance with deviations from predicted rates from 0.2 to 1.6% (Finegood et al.) and from 0.1 to 8.2% (DeBodo et al.). Use of a 0.75 pool fraction most closely approximated predicted rates.

Adult↗
PubMed1997

Human kidney free fatty acid and glucose uptake: evidence for a renal glucose-fatty acid cycle.

To determine the relationship between free fatty acids (FFA) and glucose uptake by the human kidney, 12 postabsorptive normal volunteers underwent renal vein catheterization and were infused to isotopic steady state with [6-3H]glucose and [9,10-3H]palmitate. Arterial and renal vein palmitate specific activities were not significantly different (3,533 +/- 219 vs. 3,549 +/- 220 dpm/mumol, P = 0.64). Palmitate renal fractional extraction and uptake determined isotopically (7.2 +/- 1.1% and 9.1 +/- 1.4 mumol/min) were not significantly different from those calculated by net balance measurements (8.3 +/- 1.2% and 9.7 +/- 1.2 mumol/min, P > 0.07 and P > 0.7, respectively). Renal palmitate uptake accounted for 8.7 +/- 1.3% of its systemic turnover. Renal linoleate and oleate fractional extraction calculated by net balance measurements (8.0 +/- 0.9 and 7.7 +/- 1.2%, respectively) were not significantly different from each other and that of palmitate (all P > 0.7). Renal uptake of palmitate, linoleate (7.9 +/- 1.0 mumol/min), and oleate (10.9 +/- 2.0 mumol/min) were all directly proportional to their arterial concentrations (r = 0.70, 0.68, and 0.63, respectively, all P < 0.025). Renal glucose uptake (93 +/- 10 mumol/min) accounted for 12.6 +/- 1.5% of its systemic turnover and was inversely related to the sum of palmitate, linoleate, and oleate uptake (r = -0.74, P < 0.01). These data indicate that in postabsorptive humans: 1) the kidney is an important site of FFA and glucose disposal, 2) a renal glucose-fatty acid cycle may exist, and 3) there appears to be little or no release into the circulation of stored renal FFA.

Adult↗
PubMed1997

Features of malignancy in a benign pheochromocytoma.

Pheochromocytomas are rare conditions with a prevalence of 1-2/100,000 in the general population and 1/1,000 hypertensive subjects [1]. 10% of pheochromocytomas are malignant and various attempts have been made to find useful prognostic indicators of malignancy. In general, increased plasma or urine dopamine concentrations or increased homovanillic acid excretion and lack of 131-methyliodo-benzylguanidine uptake have been associated with malignancy [2]. However, to date no specific metabolic, radiologic or histopathologic features of either benign or malignant pheochromocytomas allowing the safe diagnosis of one or the other have been identified. The diagnosis of malignant pheochromocytoma can be made only in the presence of local tissue invasion or distant metastases. We present a benign pheochromocytoma exhibiting several features suggestive of malignant disease.

Adult↗
PubMed1996

Glutamine and alanine metabolism in NIDDM.

Gluconeogenesis is increased in NIDDM. We therefore examined the metabolism of glutamine and alanine, the most important gluconeogenic amino acids, in 14 postabsorptive NIDDM subjects and 18 nondiabetic volunteers using a combination of isotopic ([6-3H]glucose (20 microCi, 0.2 microCi/min), [U-14C]glutamine (20 microCi, 0.2 microCi/min), [3-13C]alanine (99% 13C, 2 mmol, 20 micromol/min), [ring-2H5]phenylalanine (99% 2H, 2 micromol/kg, 0.03 micromol x kg(-1) x min(-1)), and limb balance techniques. Alanine turnover (4.54 +/- 0.24 vs. 5.64 +/- 0.33 micromol x kg(-1) x min(-1)), de novo synthesis (3.00 +/- 0.25 vs. 4.01 +/- 0.33 micromol x kg(-1) x min(-1)), and conversion to glucose (1.02 +/- 0.09 vs. 1.56 +/- 0.17 micromol x kg(-1) x min(-1)) were increased in NIDDM subjects (all P < 0.01), while its forearm release (0.45 +/- 0.04 vs. 0.39 +/- 0.04 micromol x kg(-1) x min(-1)) was unaltered. Although glutamine turnover (4.81 +/- 0.23 vs. 4.40 +/- 0.31 micromol x kg(-1) x min(-1)) was unaltered in NIDDM, its conversion to glucose (0.57 +/- 0.04 vs. 1.08 +/- 0.10 micromol x kg(-1) x min(-1)) and to alanine (0.10 +/- 0.01 vs. 0.34 +/- 0.04 micromol x kg(-1) x min(-1)) (both P = 0.001) was increased while its oxidation (2.84 +/- 0.27 vs. 1.84 +/- 0.15 micromol x kg(-1) x min(-1), P = 0.03) and forearm release (0.77 +/- 0.05 vs. 0.62 +/- 0.09 micromol x kg(-1) x min(-1), P < 0.008) were both reduced. Our results thus demonstrate that there are substantial alterations of glutamine and alanine metabolism in NIDDM. Conversion of both amino acids to glucose and the proportion of their turnover used for gluconeogenesis are increased; release of both amino acids from tissues other than skeletal muscle seems to be increased. Finally, the reduction in glutamine oxidation, possibly the result of competition with glucose and free fatty acids as fuels, makes more glutamine available for gluconeogenesis without a change in its turnover.

Alanine↗
PubMed1995

Metabolic effects of metformin in non-insulin-dependent diabetes mellitus.

BACKGROUND: The metabolic effects and mechanism of action of metformin are still poorly understood, despite the fact that it has been used to treat patients with non-insulin-dependent diabetes mellitus (NIDDM) for more than 30 years. METHODS: In 10 obese patients with NIDDM, we used a combination of isotope dilution, indirect calorimetry, bioimpedance, and tissue-balance techniques to assess the effects of metformin on systemic lactate, glucose, and free-fatty-acid turnover; lactate oxidation and the conversion of lactate to glucose; skeletal-muscle glucose and lactate metabolism; body composition; and energy expenditure before and after four months of treatment. RESULTS: Metformin treatment decreased the mean (+/- SD) glycosylated hemoglobin value from 13.2 +/- 2.2 percent to 10.5 +/- 1.6 percent (P < 0.001) and reduced fasting plasma glucose concentrations from 220 +/- 41 to 155 +/- 28 mg per deciliter (12.2 +/- 0.7 to 8.6 +/- 0.5 mmol per liter) (P < 0.001). Although resting energy expenditure did not change, the patients lost 2.7 +/- 1.3 kg of weight (P < 0.001), 88 percent of which was adipose tissue. The mean (+/- SE) rate of plasma glucose turnover (hepatic glucose output and systemic glucose disposal) decreased from 2.8 +/- 0.2 to 2.0 +/- 0.2 mg per kilogram of body weight per minute (15.3 +/- 0.9 to 10.8 +/- 0.9 mumol per kilogram per minute) (P < 0.001), as a result of a decrease in hepatic glucose output; systemic glucose clearance did not change. The rate of conversion of lactate to glucose (gluconeogenesis) decreased by 37 percent (P < 0.001), whereas lactate oxidation increased by 25 percent (P < 0.001). There were no changes in the plasma lactate concentration, plasma lactate turnover, muscle lactate release, plasma free-fatty-acid turnover, or uptake of glucose by muscle. CONCLUSIONS: Metformin acts primarily by decreasing hepatic glucose output, largely by inhibiting gluconeogenesis. It also seems to induce weight loss, preferentially involving adipose tissue.

Blood Glucose↗
PubMed1995

Estimation of glucose-alanine-lactate-glutamine cycles in postabsorptive humans: role of skeletal muscle.

To evaluate transfer of carbon between plasma glucose and plasma alanine (glucose-alanine cycle) and lactate (Cori cycle), to assess the contribution of skeletal muscle to these cycles, and to determine whether a glucose-glutamine cycle exists in postabsorptive humans, we infused 11 normal overnight-fasted volunteers with [2-3H]glucose, [6-14C]glucose, and [3-13C]alanine to isotopic steady state and in 7 of these simultaneously measured forearm net balance, uptake, and release of labeled and unlabeled glucose, lactate, and alanine. We found that 40.9 +/- 3.3, 66.8 +/- 3.2, and 13.4 +/- 1.1%, respectively, of plasma alanine, lactate, and glutamine carbon came from plasma glucose. More plasma glucose was converted to plasma alanine than could be derived from plasma alanine (1.89 +/- 0.20 vs. 1.48 +/- 0.15 mumol.kg-1.min-1, P < 0.001). A similar direction of net carbon flux was found for lactate (8.5 vs. 4.2 mumol.kg-1.min-1), with only glutamine adding more carbon to plasma glucose than was received from it (1.0 vs. 0.75 mumol.kg-1.min-1). Skeletal muscle accounted for 50.2 +/- 3.9 and 45.5 +/- 5.7% of the overall appearance of alanine and lactate in plasma and 54.2 +/- 5.4 and 36.4 +/- 4.2% of their respective origins from plasma glucose. Skeletal muscle release of alanine and lactate that had been formed from plasma glucose accounted for 19.1 +/- 2.1 and 48.4 +/- 4.8%, respectively, of muscle glucose uptake and 42.4 +/- 5.5 and 49.9 +/- 5.8% of the overall release of alanine and lactate from muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Diagnostic considerations in pheochromocytoma and chronic hemodialysis: case report and review of the literature.

We present a patient on long-term hemodialysis (LTH) discovered to have a pheochromocytoma. A thorough workup pertaining his catecholamine status was performed, and intraoperative catecholamine changes were monitored. This condition poses some analytical difficulties as both interpretation of plasma catecholamine measurements and determination of their metabolic products are impaired. The literature about catecholamines with respect to hemodialysis is reviewed, and the known cases of pheochromocytoma in LTH patients are discussed. Predialysis norepinephrine concentrations were almost consistently elevated though less than 3-fold when compared to normal controls. Epinephrine is not significantly different in both groups. At least a 3.3-fold increase of epinephrine or norepinephrine in LTH patients with adrenal pheochromocytomas is observed. We conclude that plasma epinephrine elevations can be evaluated in the conventional manner, and norepinephrine concentrations beyond a 3-fold elevation should raise the suspicion of a pathological catechol excess syndrome. The interpretation of plasma homovanillic acid and vanillylmandelic acid in this condition is complicated by the lack of data in LTH patients without pheochromocytoma. Markedly elevated baseline concentrations for these parameters are assumed.

Adrenal Gland Neoplasms↗
PubMed1995

Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon transport in man.

To compare glutamine and alanine as gluconeogenic precursors, we simultaneously measured their systemic turnovers, clearances, and incorporation into plasma glucose, their skeletal muscle uptake and release, and the proportion of their appearance in plasma directly due to their release from protein in postabsorptive normal volunteers. We infused the volunteers with [U-14C] glutamine, [3-13C] alanine, [2H5] phenylalanine, and [6-3H] glucose to isotopic steady state and used the forearm balance technique. We found that glutamine appearance in plasma exceeded that of alanine (5.76 +/- 0.26 vs. 4.40 +/- 0.33 mumol.kg-1.min-1, P < 0.001), while alanine clearance exceeded glutamine clearance (14.7 +/- 1.3 vs. 9.3 +/- 0.8 ml.kg-1.min-1, P < 0.001). Glutamine appearance in plasma directly due to its release from protein was more than double that of alanine (2.45 +/- 0.25 vs. 1.16 +/- 0.12 mumol.kg-1.min-1, P < 0.001). Although overall carbon transfer to glucose from glutamine and alanine was comparable (3.53 +/- 0.24 vs 3.47 +/- 0.32 atoms.kg-1.min-1), nearly twice as much glucose carbon came from protein derived glutamine than alanine (1.48 +/- 0.15 vs 0.88 +/- 0.09 atoms.kg-1.min-1, P < 0.01). Finally, forearm muscle released more glutamine than alanine (0.88 +/- 0.05 vs 0.48 +/- 0.05 mumol.100 ml-1.min-1, P < 0.01). We conclude that in postabsorptive humans glutamine is quantitatively more important than alanine for transporting protein-derived carbon through plasma and adding these carbons to the glucose pool.

Alanine↗
PubMed1995

Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine.

Despite ample evidence that the kidney can both produce and use appreciable amounts of glucose, the human kidney is generally regarded as playing a minor role in glucose homeostasis. This view is based on measurements of arteriorenal vein glucose concentrations indicating little or no net release of glucose. However, inferences from net balance measurements do not take into consideration the simultaneous release and uptake of glucose by the kidney. Therefore, to assess the contribution of release and uptake of glucose by the human kidney to overall entry and removal of plasma glucose, we used a combination of balance and isotope techniques to measure renal glucose net balance, fractional extraction, uptake and release as well as overall plasma glucose appearance and disposal in 10 normal volunteers under basal postabsorptive conditions and during a 3-h epinephrine infusion. In the basal postabsorptive state, there was small but significant net output of glucose by the kidney (66 +/- 22 mumol.min-1, P = 0.016). However, since renal glucose fractional extraction averaged 2.9 +/- 0.3%, there was considerable renal glucose uptake (2.3 +/- 0.2 mumol.kg-1.min-1) which accounted for 20.2 +/- 1.7% of systemic glucose disposal (11.4 +/- 0.5 mumol.kg-1.min-1). Renal glucose release (3.2 +/- 0.2 mumol.kg-1.min-1) accounted for 27.8 +/- 2.1% of systemic glucose appearance (11.4 +/- 0.5 mumol.kg-1.min-1). Epinephrine infusion, which increased plasma epinephrine to levels observed during hypoglycemia (3722 +/- 453 pmol/liter) increased renal glucose release nearly twofold (5.2 +/- 0.5 vs 2.8 +/- 0.1 mol.kg-1.min-1, P = 0.01) so that at the end of the infusion, renal glucose release accounted for 40.3 +/- 5.5% of systemic glucose appearance and essentially all of the increase in systemic glucose appearance. These observations suggest an important role for the human kidney in glucose homeostasis.

Adult↗
PubMed1994

Glycogen: its mode of formation and contribution to hepatic glucose output in postabsorptive humans.

To assess the relative contributions of gluconeogenesis and glycogenolysis to overall hepatic glucose output in postabsorptive normal humans and those of the indirect and direct pathways for glycogen synthesis, we studied six normal volunteers, who had been fasted for 16 h to reduce their hepatic glycogen stores, and then ingested glucose (250 g over 10 h) enriched with [6-3H] glucose to replenish and label their hepatic glycogen. After a 10-h overnight fast, release of the [6-3H] glucose into the circulation was traced with [2-3H] glucose to estimate breakdown of glycogen that had been formed via the direct pathway while gluconeogenesis was simultaneously estimated by incorporation of infused [14C] lactate into plasma glucose. We found that release of [6-3H] glucose into plasma (6.79 +/- 0.69 mumol.kg-1.min-1) accounted for 46 +/- 5% of hepatic glucose output (15.0 +/- 0.7 mumol.kg-1.min-1) while glucose formed from lactate (2.71 +/- 0.28 mumol.kg-1.min-1) accounted for 19 +/- 2% of hepatic glucose output. Since these determinations underestimate direct pathway glycogenolysis and overall gluconeogenesis, a maximal estimate for the contribution of indirect pathway glycogenolysis to hepatic glucose output is obtained by subtracting the sum of direct pathway glycogenolysis and lactate gluconeogenesis from hepatic glucose output. This amounted to a maximum of 36 +/- 5% of hepatic glucose output and 44 +/- 6% of overall glycogenolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

Systemic vasculitis positive for circulating anti-neutrophil cytoplasmic antibodies and with predominantly neurological presentation.

A 57-year-old male patient suffering from dramatically deteriorating diffuse and focal central nervous system symptoms was admitted to hospital after a short prodromal period in a somnolent state. He was diagnosed as having systemic vasculitis positive for circulating anti-neutrophil cytoplasmic antibodies, primarily involving the brain, but also most other organ systems. Circulating anti-neutrophil cytoplasmic antibodies are highly specific for Wegener granulomatosis, though they have been detected in rare cases of other vasculitic syndromes. Central nervous system lesions as presenting signs in Wegener granulomatosis have to be regarded as rare. This case nonetheless suggests that Wegener granulomatosis has to be considered in patients with a predominantly cerebral manifestation of a vasculitic syndrome.

Antibody Specificity↗
PubMedDate not supplied

Relationship between serum adiponectin concentration and intramyocellular lipid stores in humans.

The recently identified adipocytokine adiponectin has been shown to improve insulin action and decrease triglyceride content in skeletal muscle (by stimulating lipid oxidation) in mice. In the present study, we tested the hypothesis that high serum concentrations of adiponectin are associated with lower intramyocellular (IMCL) fat content by promoting lipid oxidation in humans. IMCL-content in predominantly non-oxidative tibialis anterior muscle and oxidative soleus was determined by proton magnetic resonance spectroscopy in a cross- sectional study involving 63 healthy volunteers. In a second set of experiments, changes in IMCL in both muscles were measured after a three days dietary lipid challenge (n = 18) and after intravenous lipid challenge (n = 12) with suppressed lipid oxidation under hyperinsulinemia. Adiponectin serum concentrations were found to be negatively correlated with IMCL in the oxidative soleus muscle (IMCL [sol]) (r = - 0.46, p < 0.001) independent of measures of obesity, but not with IMCL in the non-oxidative tibialis anterior muscle (IMCL [tib]) (p = 0.40). Adiponectin serum concentrations were negatively correlated with the observed increase in IMCL load after dietary lipid challenge in the tibialis (r = 0.53, p = 0.03) but not in the soleus muscle. During suppression of lipid oxidation by hyperinsulinemia, no effect of adiponectin on IMCL was observed in either soleus or tibialis muscle. Overall, the presented findings are consistent with the hypothesis that adiponectin promotes lipid oxidation in humans resulting in lower intracellular lipid content in human muscle. These results are consistent with animal data, where adiponectin could be shown to enhance lipid oxidation and reduce muscle triglycerides.

Adiponectin↗