An in vitro human muscle preparation suitable for metabolic studies. Decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects.

We have developed an in vitro muscle preparation suitable for metabolic studies with human muscle tissue and have investigated the effects of obesity and non-insulin-dependent diabetes mellitus (NIDDM) on glucose transport. Transport of 3-O-methylglucose and 2-deoxyglucose was stimulated approximately twofold by insulin in muscle from normal nonobese subjects and stimulation occurred in the normal physiological range of insulin concentrations. In contrast to insulin stimulation of 3-O-methylglucose and 2-deoxyglucose transport in muscle from normal, nonobese subjects, tissue from morbidly obese subjects, with or without NIDDM, were not responsive to insulin. Maximal 3-O-methylglucose transport was lower in muscle of obese than nonobese subjects. Morbidly obese patients, with or without NIDDM, have a severe state of insulin resistance in glucose transport. The novel in vitro human skeletal muscle preparation herein described should be useful in investigating the mechanism of this insulin resistance.

IGF-I--stimulated glucose transport in human skeletal muscle and IGF-I resistance in obesity and NIDDM.

Based on the observation that insulinlike growth factor I (IGF-I) can stimulate glucose utilization in nondiabetic subjects and that the action of the IGF-I receptor is normal in the skeletal muscle of patients with non-insulin-dependent diabetes mellitus (NIDDM), it seems possible that IGF-I might provide an effective acute treatment for the hyperglycemia of NIDDM. Using our recently developed in vitro human muscle preparation, we investigated the hypothesis that IGF-I might be an effective alternative to insulin in stimulating glucose transport in diabetic muscle. Abdominal muscle samples from nonobese nondiabetic, obese nondiabetic, and obese NIDDM patients were obtained during elective abdominal surgery. Plasma levels of IGF-I in diabetic patients were lower than those in either of the nondiabetic groups. Binding studies with wheat-germ-agglutinin-chromatography-purified receptors demonstrated the presence of IGF-I receptors in human muscle, with IGF-I binding being approximately 24% that of insulin. There was no change in IGF-I binding in muscle from obese or diabetic subjects, and the structural characteristics of the IGF-I receptor were not altered, as determined by electrophoretic mobility. IGF-I stimulated glucose transport approximately twofold in incubated muscle from control subjects, but there was no IGF-I stimulation of transport in muscle from obese subjects with or without NIDDM. These results confirm a previous report that human muscle contains receptors for IGF-I and demonstrate for the first time that IGF-I can stimulate glucose transport in human muscle. However, muscle from obese subjects with or without NIDDM is resistant to the action of IGF-I.

An AutoAnalyzer method for estimating serum glyceride glycerol using a glycerokinase procedure.

THE GLYCERIDE GLYCEROL ANALYSIS DEPENDS, AFTER SAPONIFICATION OF TRIGLYCERIDES, ON A LINKED ENZYMATIC PROCEDURE USING GLYCEROKINASE, PYRUVATE KINASE, AND LACTATE DEHYDROGENASE: the final conversion of NADH to NAD(+) is followed fluorimetrically. Twenty analyses can be performed per hour on the AutoAnalyzer; recoveries of added triglycerides ranged between 90 and 104%. In a mixed male and female group the normal range for glyceride glycerol was 2.5 to 15.5 mg/100 ml (0.2-1.4 mmol/l) fasting, and 2.5 to 18.0 mg/100 ml (0.2-1.6 mmol/l) postprandially using fresh serum. There was a significant rise postprandially in older men.

Vaginal hysterectomy for sterilization.

PIP: Vaginal hysterectomy for sterilization was performed on 115 patients. The Heaney technique was used by nine gynecologists, using lidocaine and adrenaline. The average age of patients was 32.2 years and average parity 3.2. Significant unsuspected pathology was found after surgery in 21 patients. One postoperative death occurred due to a brain stem infarction. Complications after hospitalization were vaginal cuff bleeding and urinary tract infection. Lowered morbidity of patients on oral contraceptives was significant but morbidity in patients with IUD's in place was not statistically significant. Vaginal hysterectomy is recommended for elective sterilization.^ieng

Failure of accentuated vertical body movements to induce cardiac-locomotor coupling.

Cardiac-locomotor coupling (CLC) has been reported during a variety of rhythmic human activities. One reason postulated for such coupling is that axial movements of the viscera during some activities (the "visceral piston") may enhance expulsion of blood from the heart; if so, accentuated vertical movements of the body should provide a powerful stimulus to coupling. To test this hypothesis, we studied 20 subjects hopping and 20 others skipping rope for greater than or equal to 10 min while electrocardiographic and force-platform signals were recorded, from which we derived the subjects' exercise and heart rates. The incidence and intensity of apparent coupling in the test subjects were compared with those of cross-over controls, where the heart rate of each subject was related to the hopping or skipping rate of a matched subject. Ratios consistent with coupling were seen in 10 (50%) hopping subjects under test conditions and in 13 (65%) under control conditions; among skipping subjects, the incidences were 11 (55%) and 10 (50%). In neither group of subjects was the difference in the incidences or the intensities of apparent CLC statistically significant. Our failure to detect CLC while our subjects were hopping or skipping suggests that the visceral piston is unimportant to the CLC phenomenon.

The structure of the investment tax credit.

Since the introduction as a tax incentive to encourage capital investment credit has been repeated, reinstated and modified several times. In essence, the ITC provides a credit against the taxes of an institution purchasing qualified equipment. The amount of the credit percentage has varied over the years, but the Revenue Act of 1978 made the percentage permanent at 10%.

Static and dynamic forward stability of occupied wheelchairs: influence of elevated footrests and forward stabilizers.

With 20 able-bodied subjects, three hypotheses were tested: (1) that elevating the footrests reduces the forward stability of occupied wheelchairs, (2) that placing simulated plaster casts on the occupant's legs further reduces stability, and (3) that forward stabilizers limit the extent of dynamic forward instability. Static stability was studied on a tilting platform; dynamic stability was tested by having subjects descend a ramp. Elevating one or both footrests and adding one or two simulated casts each significantly reduced static forward stability. During dynamic testing with lowered footrests, only seven subjects tipped forward, and the extent of tip was limited by the footrests. With both footrests elevated, eight subjects tipped transiently, and 12 continued to tip until the footrests hit the floor. With the addition of simulated casts, all 20 subjects tipped fully. Elevating one footrest (with or without a cast) caused only transient tips. On a high-friction floor surface, 19 and 18 subjects (with and without casts) experienced full tips or yawing falls to the side of the elevated footrest. The addition of forward stabilizers prevented wheelchairs from full tips or falls, when the users had both legs elevated, or when one of the users' legs (p less than 0.005), was elevated while located on a high friction floor (p less than 0.005). These findings have implications for wheelchair design and prescription.

Decreased expression of glucose transporter in muscle from insulin-resistant patients.

We have observed that in vitro incubated human muscle fiber strips from obese patients with or without non-insulin-dependent diabetes mellitus (NIDDM) have reduced insulin-stimulated glucose transport rates compared with nonobese control patients. To investigate if the decrease in glucose transport is associated with a depletion of glucose transport protein, we performed Western blot analysis of muscle samples from nonobese control, obese nondiabetic, and obese NIDDM patients to measure the levels of the muscle-adipose tissue glucose transporter (GLUT-4) protein. Glucose transporter protein was depressed by 23% in the obese nondiabetic and 18% in the obese NIDDM group. The results were essentially the same in the rectus abdominus and vastus lateralis muscles. These data suggest that the decreased glucose transport rate observed in muscle of these obese patients with or without NIDDM may be due, at least in part, to a decreased expression of the "insulin-sensitive" (GLUT-4) glucose transporter. This alteration may play a role in the insulin resistance seen in obesity and diabetes.

Muscle insulin resistance in uremic humans: glucose transport, glucose transporters, and insulin receptors.

To determine the cellular basis for insulin resistance observed in patients with uremia, we investigated insulin action in vivo and in vitro using skeletal muscle obtained from patients with chronic renal failure. Uremic subjects had significantly reduced rates of insulin-stimulated glucose disposal, as determined by a 3-h intravenous glucose tolerance test and using the hyperinsulinemic euglycemic clamp technique. Hepatic glucose production was similar before (control, 76.2 +/- 6.3 vs. uremic, 74.2 +/- 6.9 mg.kg-1.min-1) and during insulin infusion at 40 mU.m-2.min-1 (control, -60.9 +/- 6.6 vs. uremic, -53.9 +/- 6.3 mg.kg-1.min-1). In incubated human skeletal muscle fiber strips, basal 2-deoxy-D-glucose transport was unchanged in uremic subjects compared with controls. However, the increase in insulin-stimulated glucose transport was significantly reduced by 50% in muscles from uremic patients (P = 0.012). In partially purified insulin receptors prepared from skeletal muscle, 125I-labeled insulin binding, beta-subunit receptor autophosphorylation, and tyrosine kinase activity were all unchanged in uremic subjects. The abundance of insulin-sensitive (muscle/fat, GLUT-4) glucose transporter protein measured by Western blot using Mab 1F8 or polyclonal antisera was similar in muscles of control and uremic patients. These findings suggest that the insulin resistance observed in skeletal muscle of uremic patients cannot be attributed to defects in insulin receptor function or depletion of the GLUT-4 glucose transporter protein. An alternative step in insulin-dependent activation of the glucose transport process may be involved.