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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alternative substrates other than glucose could be used by the brain. In this study we hypothesized that lactate and ketone bodies can provide a significant portion of oxidative brain substrates in insulin-dependent diabetes mellitus (IDDM). Six control (C) and six insulin-treated streptozotocin diabetic (IDDM) dogs were studied during euglycemia (EU) and acute insulin induced hypoglycemia (HYPO). During EU for similar plasma glucose concentration (5.5 +/- 0.4 v 5.2 +/- 0.2 mmol/L in IDDM dogs showed a higher baseline lactate concentration (1.5 +/- 0.25 v 0.74 +/- 0.10 mmol/L; P less than .05). The ketone body concentrations were also increased in IDDM dogs but this increase was not statistically significant. The brain glucose uptake was 6.9 +/- 0.6 mumol/kg/min in C and 5.4 +/- 0.7 in IDDM. Lactate was released by the brain both in IDDM dogs (11.36 +/- 1.8 mumol/kg/min) and in C dogs (3.87 +/- 0.9; P less than .05). The brain ketones rate of disappearance (Rd) was 0.3 +/- 0.05 mumol/kg/min in IDDM dogs and 0.19 +/- 0.08 in C dogs. During HYPO the glucose uptake across the brain was 2.88 +/- 0.7 mumol/kg/min in IDDM and 3.12 +/- 0.5 in C dogs. We observed an overall brain lactate release (3.21 +/- 1.7 mol/kg/min) in C dogs and a net uptake (13.44 +/- 1.1; P less than .01) in IDDM (P less than .01). The brain ketones Rd was 0.1 +/- 0.2 mumol/kg/min in IDDM and 0.1 +/- 0.1 in C dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substrate availability other than glucose in the brain during euglycemia and insulin-induced hypoglycemia in dogs. 240 19

Fetal hyperinsulinemia causes fetal arterial hypoxia because fetal O2 use increases, whereas the supply of O2 to the fetus does not. To find which of the fetal tissues accounts for such an increase in fetal O2 use, we examined the effect of plasma hyperinsulinemia on O2, glucose, and lactate use by the hindquarters of 13 fetal sheep. Spinal anesthesia was used for the ewes, and local anesthesia was used for the fetuses during placement of catheters. The ewes then recovered for 5 days. After 18 h of insulin infusion, blood samples were drawn, and microspheres were injected to measure blood flow to the tissues of the hindquarters. Three to five infusions of various insulin concentrations in each fetus were followed by blood sampling and blood-flow measurements. Fetal hyperinsulinemia (less than or equal to 437 pM) increased blood flow to and O2 use by the hindquarters of the fetal sheep but did not affect the glucose-O2 quotients of these tissues. Consequently, glucose use increased proportionately to the increased O2 use. Lactate production was not affected by insulin. We conclude that increased O2 use by all the nonvisceral fetal tissues accounted for the increased O2 use of the entire fetus reported during fetal hyperinsulinemia and, consequently, for the fetal arterial hypoxemia associated with fetal hyperinsulinemia. If the hyperinsulinemic human fetus (such as the infant of the diabetic mother) also increases O2 use in nonvisceral tissue, such an increase might contribute to the susceptibility of the infants to late intrauterine fetal death, polycythemia, and hyperbilirubinemia, all of which may be consequences of intrauterine arterial hypoxemia.
Diabetes 1989 May
PMID:Effect of insulin on metabolism of fetal sheep hindquarters. 265 30

The present study examined the effect of the aldose reductase inhibitor Statil (ICI 128436, ICI, Cheshire, U.K.) on the levels of metabolites and activities of enzymes involved in the glycolysis, polyol pathway and pentose phosphate pathway and on the flux of radioactive glucose through these pathways in kidney of streptozotocin diabetic rats. In kidneys of diabetic rats of 30 days duration the level of sorbitol was increased by +82% and fructose concentration was raised by +42%. After treatment with Statil for 9 days (reversal study) a significant fall in kidney sorbitol concentration and kidney fructose concentration was found. Lactate and UDP-glucose concentrations which were both significantly raised in diabetes by +80% and +23% respectively decreased by 20% after Statil treatment, together with a decline in UDP-glucose dehydrogenase activity. Aldose reductase and sorbitol dehydrogenase activities were also significantly lowered by Statil. In the reversal study there was no significant effect of Statil on the flux of glucose via alternative routes in the kidney cortex. In kidneys of diabetic rats of 9 days duration, the level of sorbitol increased by +61% and the concentration of fructose was raised by +30%. The treatment with Statil (25 mg/kg) from the day of induction of diabetes (prevention study) prevented the accumulation of sorbitol, fructose and UDP-glucose. The increase in the incorporation of radioactive glucose through the pentose phosphate pathway seen in diabetes was less marked in the renal cortex of diabetic rats treated with Statil ab initio.
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PMID:The effect of aldose reductase inhibitor Statil (ICI 128436) on the glucose over-utilization in kidney of diabetic rats. 296 32

We have developed a new tumor marker based on the finding that cancerous sera suppress glucose utilization by cultured macrophages. Phosphofructokinase (PFK) was identified as susceptible enzyme [Naknamura et al.: JNCI 1986; 77 (in press)]. We found a high correlation between PFK inhibition and the lower buffering capacity of cancerous sera against an ATP aqueous solution and diluted acidic solutions. Sera from healthy donors changed to the PFK-suppressive type when exposed to lactate, even when followed by elimination of lactate. Lactate in cancerous sera was 1.6 times more than in normal sera. Sera from patients who tend to show acidosis, such as those with diabetes mellitus or chronic renal failure and pregnant women, also showed a lower buffering capacity as well as a higher inhibition of PFK. Although the pH method is simpler, we recommend the application of the PFK inhibition test, because this enzyme inhibition is not simply composed of a lower buffering capacity of cancerous sera, but partially of an inactivation of the enzyme through oxidation.
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PMID:Decrease of serum buffering capacity associated with malignant neoplasms. 297 97

Figure 18 outlines a summary of the results obtained in our laboratory and how these might be interpreted. Following a 100-g oral glucose load, about 25 g is taken up by the liver. About 5 g or 5% of this would be removed on a first-pass basis since only about a fifth of the portal vein glucose is newly absorbed. The remainder of the glucose is disposed of in peripheral tissues. This disposal is enhanced by intestinal insulinotropic factors that stimulate insulin secretion. Lactate is produced peripherally (with the red cells as one of the most important sources) by the gut and, perhaps, by hepatocytes. It is taken up by gluconeogenetic hepatocytes to form glycogen. This pathway appears to account for half to two-thirds of glycogen synthesis, the remainder being by direct uptake of glucose. The gluconeogenetic pathway of glycogen formation may be important in that it clears the obligatory production of lactate from certain tissues. The only difference between intravenous and oral glucose loading is that there is no absorbed glucose in the portal vein when glucose is infused. The glucose concentrations here are, however, almost the same as during oral glucose loading since peripheral clearance of glucose is slower in the absence of insulinotropic intestinal factors. This helps to explain why liver handling of intravenous glucose and glycogen formation are almost identical to the case of oral loading.
Diabetes Metab Rev 1987 Jan
PMID:Tracer methods and the metabolic disposal of a carbohydrate load in man. 356 79

Diabetes mellitus is associated with important changes in renal hemodynamics. The purpose of this study was to determine whether an increase in blood concentration patterns of ketone bodies and lactic acid, organic acids often elevated in poorly controlled insulin-dependent diabetes mellitus (IDDM), could contribute to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) regardless of changes in circulating levels of glucose and insulin. Six IDDM patients and six normal subjects were given a saline infusion (15 mumol.min-1.kg-1) for 2 h, an acetoacetic acid infusion (15 mumol.min-1.kg-1) for another 2 h, and then a saline infusion after an overnight fast during euglycemic insulin-glucose clamp. Acetoacetic acid infusion resulted in an increase of blood ketone bodies in the range of 0.7-1.5 mM from a basal value of 0.1-0.3 mM. GFR was 125 +/- 16 and 136 +/- 17 ml.min-1.1.73 m-2 in normal and IDDM subjects, respectively, during baseline saline infusion and 138 +/- 21 (P less than .01 vs. basal level) and 158 +/- 15 ml.min-1.1.73 m-2 (P less than .001 vs. basal level) during acetoacetic acid infusion. During the last saline infusion, renal hemodynamic patterns decreased again to baseline levels. Another six IDDM patients and six normal subjects were given saline, lactic acid, and saline infusions at the same rates of infusion after an overnight fast during euglycemic insulin-glucose clamp. Lactic acid concentration increased from approximately 0.5-0.8 to 1.0-1.5 mM in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Sep
PMID:Metabolic control of kidney hemodynamics in normal and insulin-dependent diabetic subjects. Effects of acetoacetic, lactic, and acetic acids. 360 98

Gestational diabetes mellitus (GDM) is a nonhomogeneous entity known to affect fetal development in different ways in both rats and human beings. The degree of severity of diabetes could affect the maternal-fetal transfer of metabolic fuels and consequently influence fetal development. To study this hypothesis, pregnant rats were made diabetic by streptozocin (STZ) treatment (45 mg/kg) at day 7 of gestation and were treated with different daily doses of insulin until the 20th day of gestation, when they were killed and examined. Differences in plasma glucose levels in the groups studied were not accompanied by differences in plasma glycerol, beta-hydroxybutyrate (beta-OHB), or total amino acid levels in mothers or their fetuses. Fetal/maternal ratios of these circulating fuels were not modified by maternal diabetes, whereas the glucose level was enhanced in diabetic rats not treated with insulin. Placental glucose transfer was studied directly with a recently reported in situ experimental design and was found to increase linearly with maternal glycemia, independently of whether this was modified by insulin treatment or by acute intravenous (i.v.) infusion of glucose in normal animals. Lactate production by the fetal/placental unit decreased in proportion to the glucose level in the maternal circulation. The present data indicate that the diabetic condition of the mother rat does not modify the mechanisms of placental transfer of metabolic fuels to the fetus, and that the actual transfer is mainly dependent on the concentrations of these fuels in the maternal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Jun
PMID:Relationship between maternal and fetal fuels and placental glucose transfer in rats with maternal diabetes of varying severity. 388 41

The euglycemic insulin clamp has been utilized extensively to measure in vivo tissue sensitivity to insulin under various circumstances. Insulin sensitivity is determined from the amount of glucose metabolized under steady state conditions. To assess the effect of abnormalities in other insulin responsive metabolic pathways on glucose metabolism and thus insulin sensitivity as measured by the glucose clamp, the concentration of lactate, pyruvate, 3-hydroxybutyrate, glycerol, alanine, and free fatty acids were measured at baseline and during a two-hour euglycemic clamp in 13 nonobese subjects with type I diabetes. The observed responses were compared to 11 normal controls. Insulin sensitivity as measured by M (glucose metabolized), MCRg (metabolic clearance of glucose), and M/I ratio (glucose metabolized per unit insulin) were all significantly decreased in the diabetic subjects (P less than 0.005). Free fatty acids (FFA) and 3-hydroxybutyrate were significantly elevated at baseline in the diabetic subjects (P less than 0.05) and decreased significantly at 60 and 120 minutes in both groups. Baseline blood pyruvate and lactate concentrations were similar in the control and diabetic subjects. Pyruvate increased significantly at 60 minutes in both groups (P less than 0.05) and returned to baseline in the control subjects but remained elevated at 120 minutes in the diabetic subjects (P less than 0.001). Lactate increased similarly in both groups and remained elevated at 60 and 120 minutes. In summary, insulin sensitivity as assessed by the euglycemic insulin clamp is decreased in type I diabetes. However, specific differences in the concentration of several other metabolites both at baseline and in response to hyperinsulinemia were also identified in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The metabolic response to the euglycemic insulin clamp in type I diabetes and normal humans. 390 Jun 31

Lactate concentrations in the cerebrospinal fluid of 104 patients were determined by the Monotest Lactate Kit. Lactate values were found higher in cases of bacterial meningitis than in patients not suffering from acute CNS disorders. Elevated lactate levels were also found in patients suffering from aseptic meningitis, septicemia, CNS trauma and cerebrovascular accidents, seizures and diabetes mellitus. The highest levels were found in cases of bacterial meningitis, but there was considerable overlapping between the groups. CSF lactate thus appears to have limited diagnostic value in the differential diagnosis between bacterial meningitis and other diseases with meningeal involvement.
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PMID:Value of CSF lactate in the differential diagnosis between bacterial meningitis and other diseases with meningeal involvement. 398 42

Lactate dehydrogenase (LDH) isoenzyme profiles in human platelets and the sera of patients with type I and II diabetes mellitus and vascular complications, as well as normal subjects were measured utilizing a recently established, modified micromethod. LDH-3 was the predominating species in platelets (37.5 +/- 3.0%), with LDH-2, 1, 4 and 5 following in decreasing order of concentration. The LDH-3/LDH-4 ratio in platelets varied from 6.2 to 1.38. Type I and type II diabetic patients with vascular complications showed a significantly higher ratio for LDH-3/LDH-4 (3.99 +/- 1.20 for DM I, 2.16 +/- 0.25 for DM II patients) than the mean ratio for normal subjects (1.14 +/- 0.08). This platelet-specific LDH isoenzyme pattern may be the result of frequent in vivo platelet-vessel wall interactions in the diabetic patients whose platelets are known to be hyperaggregable in in vitro test systems. Since non-diabetic patients patients with vascular complications also displayed a similarly elevated LDH-3/LDH-4 ratio, a wider classification is preferable, although the measurement of the LDH isoenzyme pattern will be helpful in assessing diabetic vascular complications.
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PMID:Lactate dehydrogenase isoenzymes in diabetic patients. 401 24


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