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M Ader

Publications and source records attributed to M Ader.

At least 37 records · Page 2Linked to original sources
PubMed1994

Importance of transcapillary insulin transport to dynamics of insulin action after intravenous glucose.

Insulin action in vivo is determined by both transendothelial insulin transport (TET) across the capillary and subsequent insulin binding and postreceptor events. To examine TET under non-steady-state conditions, we performed intravenous glucose tolerance tests (IVGTT; 0.3 g/kg; n = 7) on conscious dogs. At basal, insulin in lymph was only 53 +/- 7% of plasma insulin (P < 0.001), whereas lymph glucose exceeded plasma levels (109 +/- 4 vs. 104 +/- 4 mg/dl, respectively; P < 0.02). On injection, dynamics of glucose in plasma and lymph were similar, suggesting rapid equilibration of glucose between compartments. In contrast, insulin appearance in lymph was delayed relative to plasma (5.1 +/- 1.3 vs. 2 +/- 0 min), peaked later (21 +/- 2 vs. 8 +/- 2 min), attained peak value of only 52 +/- 6% of plasma insulin (range, 35-76%), and remained lower than plasma insulin throughout the IVGTT (P < 0.05 or better). Minimal model-derived insulin sensitivity (SI) averaged 3.55 +/- 0.75 x 10(-4) min-1/(microU/ml). There was a strong linear relationship between lymph insulin and its effect on glucose disappearance [X(t), r = 0.95 +/- 0.01]. Determination of the relative contributions of TET and post-TET insulin-sensitive processes to overall SI revealed that cellular sensitivity to interstitial insulin dominated (r2 = 0.55), but was not the exclusive determinant of, overall SI, as insulin transport was also important (r2 = 0.21). TET is a previously unrecognized contributor to SI in vivo.

Animals↗
PubMed1994

Dynamics of glucose production and uptake are more closely related to insulin in hindlimb lymph than in thoracic duct lymph.

We previously reported a striking similarity between the dynamics of both glucose turnover and thoracic duct lymph insulin during euglycemic clamps (J Clin Invest 84:1620, 1989), which suggested that transendothelial insulin transport (TET) is rate-limiting for insulin action in vivo. Thoracic duct lymph, however, is primarily derived from insulin-insensitive tissues, which raises questions as to the physiological significance of this relationship. The relationship between glucose turnover and TET was thus examined in insulin-sensitive tissues by the simultaneous measurement of insulin in plasma, thoracic duct lymph, and hindlimb lymph during euglycemic clamps in normal anesthetized dogs (n = 8). Clamps consisted of two 3-h phases: a 0.6 mU.min-1.kg-1 insulin infusion (activation phase) followed by termination of the insulin infusion (deactivation phase). Lymph insulin was less than plasma insulin during both phases (P < 0.01) with steady-state hindlimb (120 +/- 12 pM) and thoracic duct lymph insulin (138 +/- 12 pM) 38 and 45%, respectively, lower than steady-state plasma insulin (222 +/- 24 pM) at the end of the activation phase (P < 0.05). Also, the rate of increase of lymph insulin was slower than plasma insulin during hormone infusion; half-time to steady-state was 8.8 +/- 2.0 min for plasma insulin, but longer for thoracic (25.8 +/- 3.5) and hindlimb lymph insulin (40.7 +/- 5.7 min). A very close relationship was observed during activation between the rate of increase of glucose uptake (Rd) and the increase in hindlimb lymph insulin (r2 = 0.92); this relationship was weaker for thoracic lymph (r2 = 0.74) and much weaker between glucose uptake and plasma insulin (r2 = 0.35). These data support the concept that interstitial insulin (represented by hindlimb lymph) is the signal that determines glucose uptake by insulin-sensitive tissues and that the rate of increase of glucose uptake is determined by transendothelial insulin transport into insulin-sensitive tissue. Also, during activation, hindlimb lymph insulin was a very strong predictor of the rate of suppression of hepatic glucose output (HGO) (r2 = 0.96), and the correlation with HGO was stronger than that for thoracic lymph (r2 = 0.85). The evidence that the rate of increase of Rd and the rate of suppression of HGO during insulin infusion are very strongly predicted by the time course of insulin in hindlimb lymph is consistent with the single-gateway hypothesis: the insulin transport rate across endothelium in insulin-sensitive tissue (skeletal muscle) determines the rate of glucose utilization and the suppression of hepatic glucose output.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1992

BASREP: a method for maintaining euglycemia during somatostatin suppression of pancreatic secretion.

A glucagon infusion algorithm has been developed to reestablish basal glycemia when pancreatic insulin and glucagon secretion are inhibited by somatostatin (SRIF). When insulin alone is infused intraportally during SRIF to replace endogenous hormone release, hypoglycemia is generated by the combined actions of both peptides. In the presence of SRIF infusion, the normal physiologic response to hypoglycemia, i.e. stimulation of glucagon secretion and glucagon-induced increase in hepatic glucose production, has been prevented. Our computer algorithm, "BASREP", was designed to mimic the normal pancreatic counterregulatory response by substituting endogenous alpha-cell secretion with exogenous intraportal infusion. Sequential measurements of glucose concentration are analyzed with a minimal mathematical model of glucose disappearance, adapted to include a variable to describe glucagon stimulation of hepatic glucose production. Based upon the observed change in plasma glucose, BASREP computes after every sample the infusion rate of glucagon necessary to stimulate glucose production and maintain desired glucose level. This method minimizes instabilities and should prove useful in future investigations of glucose metabolism.

Algorithms↗
PubMed1992

Diurnal variation in glucose tolerance. Cyclic suppression of insulin action and insulin secretion in normal-weight, but not obese, subjects.

The relative roles of insulin sensitivity, insulin secretion, and glucose effectiveness to the diurnal rhythm of glucose tolerance were examined in normal-weight (n = 12) and obese (n = 11) subjects. Two frequently sampled intravenous glucose tolerance tests were performed in each subject at 0800 on one occasion and 1800 on a separate day. Tests were preceded by identical fasts of 10-12 h. In nonobese subjects, glucose tolerance, expressed as the 10- to 16-min KG value (KGs), was much reduced in the evening (AM 2.98 +/- 0.45, PM 1.86 +/- 0.33 min-1, P less than 0.002). In the obese subjects, tolerance was lower in the morning than normal-weight subjects (2.19 +/- 0.31 min-1), but unlike in nonobese subjects, tolerance was not significantly reduced during the day (1.90 +/- 0.18 min-1, P greater than 0.40). The reduction in glucose tolerance in the normal-weight subjects was caused by diminished insulin sensitivity (parameter S1, AM 15.4 +/- 2.9, PM 10.2 +/- 1.9 x 10(-5) min-1/pM, P less than 0.01) and reduced beta-cell responsivity to glucose. The evening decrease in the latter was reflected both in first-phase plasma insulin (AM 2466 +/- 441, PM 1825 +/- 381 pM/10 min, P less than 0.05) and the potentiation slope (AM 462 +/- 68, PM 267 +/- 35 pM/mM, P less than 0.01). In contrast, consistent with no diurnal variation in glucose tolerance, obese subjects exhibited no decline in insulin sensitivity in the evening (AM 3.6 +/- 0.7, PM 4.9 +/- 1.0 x 10(-5) min-1/pM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Dose-response relationship between lymph insulin and glucose uptake reveals enhanced insulin sensitivity of peripheral tissues.

To examine the role of transcapillary insulin transport to peripheral insulin sensitivity in vivo, we performed dose-response experiments in which both plasma and thoracic duct lymph insulin and glucose utilization (Rd) were measured in conscious dogs. Euglycemic clamps (n = 22) consisted of a 3-h activation period in which insulin was infused (rates: "physiological" 3.6, 5.4, 7.2 pmol.min-1.kg-1; "pharmacological" 108 pmol.min-1.kg-1), followed by a 3-h deactivation period. [14C]inulin was also infused as a diffusionary marker. Insulin sensitivity was estimated as the ED50. When based on plasma insulin, ED50 was 480 pM. However, when calculated from lymph (i.e., interstitial) insulin measurements, ED50 was 240 pM. Thus, interstitial insulin measurements reveal that insulin sensitivity of peripheral tissues is approximately twice that estimated from plasma insulin and is similar to sensitivity reported for suppression of hepatic glucose production. Furthermore, although [14C]inulin achieved equilibrium between plasma and lymph within 180 min, within the physiological range, steady state plasma insulin was higher than insulin in lymph (306 +/- 18, 474 +/- 42, and 780 +/- 60 pM vs. 180 +/- 18, 318 +/- 12, and 504 +/- 36 pM; P less than 0.0001); plasma insulin achieved steady state faster than lymph insulin (6 +/- 1, 6 +/- 2, and 11 +/- 3 min vs. 29 +/- 4, 16 +/- 6, and 44 +/- 8 min; P less than 0.01) and disappeared faster (5 +/- 2, 7 +/- 2, and 15 +/- 6 min vs. 37 +/- 8, 32 +/- 4, and 43 +/- 9 min; P less than 0.01). The time course of lymph insulin at each dose was similar to that of Rd, and at each dose, unlike plasma insulin, lymph insulin was strongly correlated with Rd (r = 0.93 or better). At pharmacological hyperinsulinemia (plasma 35232 +/- 5250 pM, lymph 27366 +/- 4380 pM), Rd rose faster than lymph insulin and disappeared more slowly than insulin. Thus, lymph insulin data indicate that the periphery is more sensitive to insulin than previously realized from estimates based solely on plasma hormone. Furthermore, lymph insulin is proportional to Rd within the physiological but not pharmacological range of insulin, indicating that transcapillary insulin transport is rate limiting for insulin action in this range. Finally, based on in vivo lymph (i.e., interstitial) insulin measurements, peripheral tissue is almost twice as sensitive to insulin than previously realized.

Animals↗
PubMed1990

Peripheral effects of insulin dominate suppression of fasting hepatic glucose production.

Insulin may suppress hepatic glucose production directly, or indirectly via suppression of release of gluconeogenic substrates from extrasplanchnic tissues. To compare these mechanisms, we performed insulin dose-response experiments in conscious dogs at euglycemia, during somatostatin infusion, and intraportal glucagon replacement. Insulin was sequentially infused either intraportally (0.05, 0.20, 0.40, 1.0, 1.4, and/or 3.0; protocol I) or systemically at half the intraportal rate (0.025, 0.10, 0.20, 0.50, 0.70, and/or 1.5 mU.min-1.kg-1; protocol II). Exogenous glucose infused during clamps was labeled with 3-[3H]glucose (2 microCi/g) to prevent a fall in plasma specific activity (P greater than 0.2) that may have contributed to previous underestimations of hepatic glucose output (HGO). Portal insulins were up to threefold higher during intraportal infusion, but peripheral insulin levels were not different between the intraportal and systemic protocols [7 +/- 5 vs. 9 +/- 1, 12 +/- 4 vs. 13 +/- 6, 16 +/- 3 vs. 27 +/- 5, 70 +/- 23 vs. 48 +/- 8, 83 +/- 3 vs. 86 +/- 21, and 128 vs. 120 +/- 14 microU/ml for paired insulin doses; P greater than 0.06 by analysis of variance (ANOVA)]. Despite higher portal insulin levels in protocol I, HGO suppression was equivalent in the two protocols when systemic insulin was matched, from 3.3 +/- 0.1 to near-total suppression at 0.3 mg.min-1.kg-1 at the highest insulin infusion rate (3.0 mU.min-1.kg-1; P less than 0.0001) with intraportal insulin, from 2.9 +/- 0.8 to -0.8 +/- 0.2 mg.min-1.kg-1 in protocol II (P less than 0.001). Suppression of HGO was similar at matched systemic insulin, regardless of portal insulin, suggesting the primacy of insulin's action on the periphery in its restraint of hepatic glucose production.

Analysis of Variance↗
PubMed1990

The role of the transcapillary insulin transport in the efficiency of insulin action: studies with glucose clamps and the minimal model.

Insulin action to augment glucose utilization (Rd) and suppress endogenous glucose production is not directly determined by changing plasma insulin, but rather by that insulin which traverses the capillary endothelial boundary to enter the interstitial space bathing insulin-sensitive cells. We have examined the importance of transcapillary insulin transport to the efficiency of insulin action by sampling insulin in thoracic duct lymph, believed to represent interstitial fluid, during euglycemic glucose clamps or intravenous glucose tolerance tests (IVGTTs) in conscious dogs. During clamps (insulin infusion: 0.6 mU/min per kg), we observed a 3:2 gradient between plasma and lymph insulin both at basal and at hyperinsulinemic steady state, which was reestablished after termination of infusion. No such gradient was observed for inulin, a non-metabolizable diffusionary marker infused along with insulin. Furthermore, lymph insulin was proportional to Rd during clamps, and these two independently measured variables were strongly correlated (r = 0.96). These results indicate that transcapillary insulin transport is rate-limiting for insulin action during clamps. Compartmental analysis of insulin and inulin data was consistent with receptor-mediated transport of insulin across capillary endothelium from plasma to interstitium. Glucose tolerance tests were subjected to minimal model analysis, which yields the insulin sensitivity index (SI) and X(t), the rate of net glucose disposition during the intravenous test. Preliminary data reveal a striking similarity between the time courses of X and measured lymph insulin during IVGTTs, evidence that interstitial insulin is virtually at equilibrium with the rate of glucose uptake. Thus, even in the non-steady state, transendothelial insulin transport is the rate determining step for insulin action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Glucose phosphorylation is not rate limiting for accumulation of glycogen from glucose in perfused livers from fasted rats.

Incorporation of Glc and Fru into glycogen was measured in perfused livers from 24-h fasted rats using [6-3H]Glc and [U-14C]Fru. For the initial 20 min, livers were perfused with low Glc (2 mM) to deplete hepatic glycogen and were perfused for the following 30 min with various combinations of Glc and Fru. With constant Fru (2 mM), increasing perfusate Glc increased the relative contribution of Glc carbons to glycogen (7.2 +/- 0.4, 34.9 +/- 2.8, and 59.1 +/- 2.7% at 2, 10, and 20 mM Glc, respectively; n = 5 for each). During perfusion with substrate levels seen during refeeding (10 mM Glc, 1.8 mumol/g/min gluconeogenic flux from 2 mM Fru), Fru provided 54.7 +/- 2.7% of the carbons for glycogen, while Glc provided only 34.9 +/- 2.8%, consistent with in vivo estimations. However, the estimated rate of Glc phosphorylation was at least 1.10 +/- 0.11 mumol/g/min, which exceeded by at least 4-fold the glycogen accumulation rate (0.28 +/- 0.04 mumol of glucose/g/min). The total rate of glucose 6-phosphate supply via Glc phosphorylation and gluconeogenesis (2.9 mumol/g/min) exceeded reported in vivo rates of glycogen accumulation during refeeding. Thus, in perfused livers of 24-h fasted rats there is an apparent redundancy in glucose 6-phosphate supply. These results suggest that the rate-limiting step for hepatic glycogen accumulation during refeeding is located between glucose 6-phosphate and glycogen, rather than at the step of Glc phosphorylation or in the gluconeogenic pathway.

Animals↗
PubMed1989

Insulin transport across capillaries is rate limiting for insulin action in dogs.

This study examined the relationship between transcapillary insulin transport and insulin action in vivo. During euglycemic clamps (n = 7) in normal conscious dogs we simultaneously measured plasma and thoracic duct lymph insulin and glucose utilization (Rd). Clamps consisted of an activation phase with constant insulin infusion (0.6 mU/kg per min) and a deactivation phase. [14C]Inulin was infused as a passively transported control substance. While [14C]inulin reached an equilibrium between plasma and lymph, steady-state (ss) plasma insulin was higher than lymph (P less than 0.05) and the ratio of 3:2 was maintained during basal, activation, and deactivation phases: 18 +/- 2 vs. 12 +/- 1, 51 +/- 2 vs. 32 +/- 1, and 18 +/- 3 vs. 13 +/- 1 microU/ml. In addition, it took longer for lymph insulin to reach ss than plasma insulin during activation and deactivation: 11 +/- 2 vs. 31 +/- 5 and 8 +/- 2 vs. 32 +/- 6 min (P less than 0.02). Rd increased from 2.6 +/- 0.1 to a ss of 6.6 +/- 0.4 mg/kg per min within 50 +/- 8 min. There was a remarkable similarity in the dynamics of insulin in lymph and Rd: the time to reach ss for Rd was not different from lymph insulin (P greater than 0.1), and the relative increases of the two measurements were similar, 164 +/- 45% and 189 +/- 29% (P greater than 0.05). While there was only a modest correlation (r = 0.78, P less than 0.01) between Rd and plasma insulin, the dynamic changes of lymph insulin and Rd showed a strong correlation (r = 0.95, P less than 0.01). The intimate relationship between lymph insulin and Rd suggests that the transcapillary insulin transport is primarily responsible for the delay in Rd. Thus, transcapillary transport may be rate limiting for insulin action, and if altered, it could be an important component of insulin resistance in obesity and diabetes mellitus.

Animals↗
PubMed1987

Insulin sensitivity in the intact organism.

Insulin resistance is a classic characteristic of type II diabetes. Precise quantification of insulin sensitivity in vivo is essential for elucidation of the pathogenesis of observed glucose intolerance. The euglycaemic glucose clamp of Andres and colleagues assesses insulin action by disrupting the negative feedback relationship of glucose and insulin. Insulin is infused, but euglycaemia is maintained by exogenous glucose infusion (GINF). At steady state, GINF (M) represents total insulin action, i.e. suppression of hepatic glucose output (HGO) plus acceleration of peripheral uptake (Rd). Coupled with the isotope dilution techniques of Steele et al, these hepatic and peripheral effects can be partitioned, although this approach may underestimate HGO and Rd. Modifications of the Steele method may be required for more reliable quantification of glucose turnover. The dose-response relationship between insulin and Rd also provides a measure of sensitivity from the glucose clamp: the ED50 (and Rdmax), analogous to the Km and Vmax of Michaelis-Menten analysis. However, extensive labour requirements, cost and difficulties in ED50 estimation limit its widespread use. Glucose clearance (Rd/G) has also been used to assess insulin sensitivity in subjects of differing glycaemia, but because it fails to rise in proportion to glucose it is an inappropriate measure. Hence, we have introduced the insulin sensitivity index SIP(clamp), defined as the action of insulin to increase glucose clearance (delta Rd/(G delta I], which is independent of prevailing glycaemia and insulinaemia. Lastly, we proposed the minimal model method, which determines insulin sensitivity (SI) from analysis of the simple intravenous glucose tolerance test (IVGTT). By adding tolbutamide injection after glucose, the resultant model-based SI is equivalent to SIP(clamp). Furthermore, minimal model analysis will also yield SG, the parameter of insulin-independent glucose disappearance. We conclude that assessment of insulin sensitivity, whilst important, must be considered in the context of its relation to pancreatic function and insulin-dependent glucose disappearance. Only a clear understanding of the complex interrelation of these factors will lead to elucidation of the mechanisms underlying glucose intolerance.

Constriction↗
PubMed1987

Recombinant deoxyribonucleic acid-derived 22K- and 20K-human growth hormone generate equivalent diabetogenic effects during chronic infusion in dogs.

Chronic administration of human GH (mol wt, 22,000; 22K-hGH) is known to generate insulin resistance in dogs. However, recent hypotheses claim that diabetogenicity may be attributable to smaller weight contaminants or fragments not found in purified lower weight hGH (mol wt, 20,000; 20K-hGH) also secreted by the pituitary. In this study, we examined the effects of chronic (12-day) low dose (0.02 mg/kg X day) infusion of recombinant DNA-derived methionyl 22K- and 20K-hGH on glucose tolerance in conscious dogs. Minimal model analysis of the frequently sampled iv glucose tolerance tests quantified insulin sensitivity and glucose effectiveness, the ability of glucose per se to normalize its own concentration. Infusion of 22K-hGH, raising plasma hGH levels to 3.8 +/- 0.6 ng/ml, resulted in an elevation in fasting glucose levels after 2 days of infusion (104 +/- 1 vs. pre-hGH 97 +/- 2 mg/dl; P less than 0.01), but the effect was transient. No change was noted during 20K-hGH treatment (P greater than 0.2). Mildly elevated fasting insulin levels were observed in both 22K- and 20K-hGH-treated dogs (P less than 0.04 and 0.03, respectively). However, despite maintenance of adequate glucose tolerance during both infusions (P greater than 0.07), marked insulin resistance was apparent; insulin sensitivity dropped from 9.7 +/- 2.4 and 11.2 +/- 2.1 X 10(-4) min-1/(microU/ml) in 22K- and 20K-hGH-treated dogs, to 2.5 and 2.8 X 10(-4) min-1/(microU/ml), a drop of 75% (P less than 0.01 and 0.001). Insulin resistance persisted throughout the infusion period, slowly returning to pre-hGH treatment levels in 22K-hGH-treated dogs during recovery. Insulin resistance persisted 3 days after cessation of 20K-hGH treatment (day 15), but returned to pre-hGH levels by day 25. Integrated glucose-stimulated insulin release was enhanced after 2 days of 22K- or 20K-hGH treatment (P less than 0.03 and less than 0.05), but the effect was transient. Maintenance of normal glucose tolerance in the face of severe insulin resistance and only transiently elevated insulin response was possible because glucose effectiveness remained unchanged. In conclusion, despite minimal effects of low dose hGH infusion on glucose tolerance and fasting glucose and insulin levels, 22K- and 20K-hGH are equipotent in generating severe insulin resistance and potentiating glucose-stimulated insulin release.

Animals↗
PubMed1985

Importance of glucose per se to intravenous glucose tolerance. Comparison of the minimal-model prediction with direct measurements.

Glucose disappearance after an oral or intravenous challenge is a function of the effects of both endogenously secreted insulin and of glucose itself. We previously introduced the term "glucose effectiveness," or SG, defined as the ability of glucose per se to enhance its own disappearance independent of an increment in plasma insulin. The present investigation, performed in conscious dogs, was undertaken to quantify this glucose effect by minimal-model-based analysis of insulin and glucose dynamics after a frequently sampled intravenous glucose tolerance test (FSIGT). The values from the standard FSIGT were then compared with direct measurements obtained from experiments in which the dynamic insulin response to glucose was suppressed with somatostatin (SRIF). In addition, we examined SG values from the modified FSIGT protocol, which involves both glucose and tolbutamide injections. Protocol l (N = 9): FSIGTs were performed and the glucose and insulin data were analyzed by computer. KG was 2.65 +/- 0.28 min-1, S1 was 4.09 +/- 0.34 X 10(4) min-1/(microU/ml), and SG was 0.033 +/- 0.004 min-1. Protocol II (N = 6): FSIGTs were performed on animals in which SRIF was infused (0.8 micrograms/min X kg) to obliterate the dynamic insulin response to glucose injection. Before the FSIGt, insulin and glucagon were infused intraportally to reattain basal glycemia. Without dynamic insulin, KG was reduced to 0.96 +/- 0.18 min-1 (P less than 0.0001). However, SG, estimated from the exponential rate of fall of plasma glucose in the absence of dynamic insulin, was similar to the standard FSIGTs: 0.025 +/- 0.004 (P greater than 0.25). Protocol III (N = 6): modified FSIGTs were performed using glucose and tolbutamide injections for a better estimate of model parameters. Model parameters Sl and SG, and the KG were not different from standard FSIGTs (P greater than 0.3). In fact, the value of SG (0.028 +/- 0.003 min-1) was nearly identical to the direct measure from protocol II. Therefore, the effect of glucose per se on glucose decline, estimated by modeling the standard and modified FSIGTs, was confirmed by a direct measurement with the endogenous insulin response suppressed with SRIF. Also, the time course of the insulin effect to enhance net glucose disappearance from plasma [Ieff(t)] was calculated from the data of protocol II, and was the same as the time course predicted by the model. These studies demonstrate the ability of the computer modeling approach to separate insulin-dependent and glucose-dependent glucose disappearance, and represent a direct confirmation of the minimal model.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Extrapancreatic effect of somatostatin infusion to increase glucose clearance.

Constant intraportal insulin, coupled with variable intraportal glucagon, was used in the attempt to reestablish basal metabolic conditions in dogs during somatostatin (SRIF) infusion (0.8 micrograms X min-1 X kg-1). SRIF alone lowered glucose (G), insulin (I), and glucagon (GN) (G: 90 +/- 5 to 69 +/- 1 mg/dl; I: 18 +/- 4 to 4 +/- 1 microU/ml; GN: 257 +/- 52 to 168 +/- 40 pg/ml; P less than 0.05 or better). Hormone replacement. Hypoglycemia persisted (G at steady state, SS, 60-150 min): 12 +/- 3 mg/dl below basal; P = 0.006) despite intraportal insulin replacement (200 microU X min-1 X kg-1; insulin at basal: 14 +/- 1; at SS: 14 +/- 2 microU/ml; P greater than 0.9) and glucagon overreplacement (basal: 341 +/- 42; SS: 486 +/- 80 pg/ml; P less than 0.05). Glucose clearance was increased 65% above basal (P less than 0.0001). Insulin underreplacement. With a lower intraportal insulin infusion rate (50 microU X min-1 X kg-1), insulin fell from basal (10 +/- 2 microU/ml) to 4 +/- 1 microU/ml during steady state (P = 0.03). Glucose and glucose clearance were normalized to basal values (G: 85 +/- 3 mg/dl, P = 0.3; clearance: 5.7 +/- 0.5 ml X min-1 X kg-1; P = 0.2) with full glucagon replacement (basal: 281 +/- 120; SS: 264 +/- 80 pg/ml; P greater than 0.9). Thus, during constant SRIF infusion, normoglycemia was reattained when insulin was underreplaced via the portal vein. The failure to reattain euglycemia with normoinsulinemia was due to a SRIF-induced increase in extrahepatic glucose clearance. Insulin replacement and growth hormone (GH) infusion. GH (15 ng X min-1 X kg-1) partially reversed the hypoglycemia during SRIF, with full insulin replacement. The SRIF-induced increase in glucose clearance may be partially mediated by a decrease in GH.

Animals↗
PubMed1983

AMP deaminase histoenzymology in hamster skeletal muscle.

A histochemical technique for AMP deaminase (E.C. 3.5.4.6) has been successfully applied in hamster skeletal muscle tissue. Indeed the hamster gastrocnemius fast-glycolytic fibers show the strongest staining for AMP deaminase while the slow-oxidative fibers present only a week staining for this histoenzymatic method. The staining appears to stain strongly the capillary endothelium as well as is clearly localized in all fiber types associated with the actomysin since the stain is observed at the level of the A-band.

AMP Deaminase↗