1,721,060 research outputs found
INSULIN-RESISTANCE AND INSULIN DEFICIENCY IN THE PATHOGENESIS OF TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS - ERRORS OF METABOLISM OR OF METHODS
No full textRole of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man
No full textPlasma FFA oxidation (measured by infusion of 14C-palmitate) and net lipid
oxidation (indirect calorimetry) are both inhibited by insulin. The present study
was designed to examine whether these insulin-mediated effects on lipid
metabolism resulted from a decline in circulating FFA levels or from a direct
action of the hormone on FFA/lipid oxidation. Nine subjects participated in two
euglycemic insulin clamps, performed with and without heparin. During each
insulin clamp study insulin was infused at two rates, 4 and 20 mU/m2.min for 120
min. The studies were performed with indirect calorimetry and 3-3H-glucose and
14C-palmitate infusion. During the control study plasma FFA fell from 610 +/- 46
to 232 +/- 42 to 154 +/- 27 mumol/liter, respectively. When heparin was infused
basal plasma FFA concentration remained constant. During the control study,
FFA/lipid oxidation rates decreased in parallel with the fall in the plasma FFA
concentration. During the insulin/heparin study, plasma 14C-FFA oxidation
remained unchanged while net lipid oxidation decreased. In conclusion, when the
plasma FFA concentration is maintained unchanged by heparin infusion, insulin has
no direct effect on FFA turnover and disposal. These results thus suggest that
plasma FFA oxidation is primarily determined by the plasma FFA concentration,
while net lipid oxidation is regulated by both the plasma FFA and the insulin
level
METABOLIC EFFECTS OF LOW-DOSE INSULIN THERAPY ON GLUCOSE-METABOLISM IN DIABETIC-KETOACIDOSIS
No full textEffect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity
No full textThe dose-response relationship between the plasma insulin concentration and
oxidative and nonoxidative pathways of free fatty acid (FFA) metabolism was
examined in 11 obese and 7 lean subjects using a stepwise insulin clamp technique
in combination with indirect calorimetry and infusion of [1-14C]palmitate. The
fasting plasma FFA concentration was elevated in obese subjects (793 +/- 43 vs.
642 +/- 39 mumol/l; P less than 0.01) and was associated with an increased basal
rate of plasma FFA turnover, FFA oxidation, and nonoxidative FFA disposal, i.e.,
reesterification (all P less than 0.01). Suppression of plasma FFA turnover by
physiological increments in plasma insulin was impaired in obese compared with
lean subjects. However, plasma FFA turnover expressed per kilogram fat mass was
normally suppressed by insulin in obese subjects. Although insulin suppressed
plasma FFA oxidation to the same extent in lean and obese subjects, inhibition of
total lipid oxidation by insulin was impaired in the obese group. Obese subjects
had an enhanced basal rate of nonoxidative FFA disposal, which was suppressed
less by physiological increments in plasma insulin compared with lean controls.
Therefore, we conclude that 1) lipolysis in uncomplicated obesity is normally
sensitive to insulin; the enhanced FFA flux is simply a consequence of the
increased fat mass. 2) Nonoxidative FFA disposal expressed per lean body mass is
enhanced in obese subjects and correlates with the increase in plasma FFA
concentration and fat mass. 3) Enhanced oxidation of intracellular lipids
contributes to the enhanced rate of total lipid oxidation in obese subjects
The role of free fatty acid metabolism in the pathogenesis of insulin resistance in obesity and noninsulin-dependent diabetes mellitus
No full textTo investigate the mechanisms of insulin resistance in obesity and
noninsulin-dependent diabetes mellitus (NIDDM), we examined oxidative and
nonoxidative pathways of free fatty acid (FFA) and glucose metabolism in 14 lean
and 17 obese (with normal oral glucose tolerance) nondiabetic subjects and in 8
lean and 8 obese subjects with NIDDM. FFA and glucose metabolism were measured
using the sequential insulin clamp technique in combination with indirect
calorimetry and infusion of [3-3H]glucose and [1-14C]palmitate. Obesity was
characterized by enlarged fat mass, which correlated positively with the plasma
FFA concentration (r = 0.62; P less than 0.01). FFA metabolism was less sensitive
to insulin in obese than in lean nondiabetic subjects, but this defect could be
overcome by increasing the plasma insulin concentration. NIDDM patients showed
normal sensitivity to the inhibitory action of insulin on FFA metabolism;
however, maximal suppression by insulin was impaired. The combination of obesity
and NIDDM was associated with a further enhancement of reesterification of FFA
than observed in either condition alone. In both obesity and NIDDM, the
dose-response curve for suppression of hepatic glucose production by insulin was impaired. While obesity was primarily characterized by reduced sensitivity to the stimulatory action of insulin on oxidative and nonoxidative pathways of glucose metabolism, resistance to the effect of insulin on glucose metabolism in NIDDM was characterized by a reduced maximal response. The combination of obesity and NIDDM further impaired the sensitivity of liver glucose output and glucose oxidation to insulin. The hypothesis is advanced that in uncomplicated obesity, increased availability and oxidation of FFA leads, by the FFA/glucose cycle, to the impairment in glucose utilization. In NIDDM, on the other hand, the defect in glucose utilization is primary, and the enhanced rate of FFA oxidation may represent a compensatory phenomenon
Effect of prolonged overnight fasting on energy metabolism in non-insulin-dependent diabetic and non-diabetic subjects
No full textThe effect on energy metabolism of a 6-h prolongation of the conventional 12-h overnight fast was examined in 9 healthy subjects and in 7 patients with non-insulin-dependent diabetes mellitus. Plasma glucose concentration decreased by 7 and 23%, in control and diabetic subjects, respectively. In control subjects, the fall in plasma glucose was associated with a slight but significant fall in plasma insulin and a rise in plasma free fatty acid concentrations. During this same period, the rates of plasma free fatty acid oxidation, measured by infusion of [14C]palmitate, and net lipid oxidation, measured by indirect calorimetry, increased in normal subjects by 55 and 76%, respectively; the rate of glucose oxidation measured by indirect calorimetry decreased by 37%. In the diabetic patients, the free fatty acid oxidation rate was enhanced already after 12 h of fasting compared with controls (2.06 vs 1.30 mumol.kg-1.min-1; p less than 0.05) and did not change significantly during the 6-h observation period. After 18 h of fasting, the rate of plasma free fatty acid oxidation was similar in control and diabetic subjects. The data thus emphasize the need for strict standardization of the overnight fasting period for metabolic studies, and demonstrate the difficulties in comparing basal rates of substrate oxidation between healthy and diabetic subjects
THE ROLE OF FREE FATTY-ACID METABOLISM IN THE PATHOGENESIS OF INSULIN RESISTANCE IN OBESITY AND NONINSULIN-DEPENDENT DIABETES-MELLITUS
No full textTo investigate the mechanisms of insulin resistance in obesity and
noninsulin-dependent diabetes mellitus (NIDDM), we examined oxidative and
nonoxidative pathways of free fatty acid (FFA) and glucose metabolism in 14 lean
and 17 obese (with normal oral glucose tolerance) nondiabetic subjects and in 8
lean and 8 obese subjects with NIDDM. FFA and glucose metabolism were measured
using the sequential insulin clamp technique in combination with indirect
calorimetry and infusion of [3-3H]glucose and [1-14C]palmitate. Obesity was
characterized by enlarged fat mass, which correlated positively with the plasma
FFA concentration (r = 0.62; P less than 0.01). FFA metabolism was less sensitive
to insulin in obese than in lean nondiabetic subjects, but this defect could be
overcome by increasing the plasma insulin concentration. NIDDM patients showed
normal sensitivity to the inhibitory action of insulin on FFA metabolism;
however, maximal suppression by insulin was impaired. The combination of obesity
and NIDDM was associated with a further enhancement of reesterification of FFA
than observed in either condition alone. In both obesity and NIDDM, the
dose-response curve for suppression of hepatic glucose production by insulin was impaired. While obesity was primarily characterized by reduced sensitivity to the stimulatory action of insulin on oxidative and nonoxidative pathways of glucose metabolism, resistance to the effect of insulin on glucose metabolism in NIDDM was characterized by a reduced maximal response. The combination of obesity and NIDDM further impaired the sensitivity of liver glucose output and glucose oxidation to insulin. The hypothesis is advanced that in uncomplicated obesity, increased availability and oxidation of FFA leads, by the FFA/glucose cycle, to the impairment in glucose utilization. In NIDDM, on the other hand, the defect in glucose utilization is primary, and the enhanced rate of FFA oxidation may represent a compensatory phenomenon
Studies on the mass action effect of glucose in NIDDM and IDDM: evidence for glucose resistance.
No full text- …
