PubMed Health⌕ Search

Biomedical subjects

L V Avioli

Publications and source records attributed to L V Avioli.

At least 91 records · Page 5Linked to original sources
PubMed1991

Bone matrix constituents stimulate interleukin-1 release from human blood mononuclear cells.

To test the hypothesis that mononuclear cells are stimulated to release interleukin 1 (IL-1) by bone fragments released in the bone microenvironment during the remodeling cycle, we have investigated the effects of bone matrix and some of its constituents on IL-1 secretin from peripheral blood mononuclear cells (PBMC). Increases in IL-1 activity were observed when either PBMC or adherent monocytes, but not lymphocytes depleted of monocytes, were co-cultured with either human or rat bone particles but not with latex particles of similar size. Co-culture of PBMC with bone particles in a transwell system where the cells were physically separated from the bone particles, or with osteoblast- or osteoclast-covered bone particles, did not stimulate IL-1 release, indicating that a physical contact between PBMC and the bone surface is required for eliciting IL-1 release. This was confirmed by the finding of a lower stimulatory effect of bone particles pretreated with etidronate, a bisphosphonate which decreases the bone binding capacity of PBMC. Constituents of bone matrix, such as collagen fragments, hydroxyproline, and, to a lesser extent, transforming growth factor-beta, but not osteocalcin, alpha 2HS glycoprotein, fragments of either bone sialoprotein or osteopontin, and fibronectin, stimulated PBMC IL-1 release in a dose-dependent fashion. Collagen-stimulated IL-1 release was partially and specifically inhibited by a monoclonal antibody directed against the alpha 2 beta 1-integrin cell surface collagen receptor. These data demonstrate that products of bone resorption, known to be chemotactic for mononuclear cells, stimulate PBMC IL-1 activity. These findings may help explain previous documentation of increased IL-1 secretion by circulating monocytes obtained from patients with high turnover osteoporosis.

Animals↗
PubMed1991

Dissociation of second messenger activation by parathyroid hormone fragments in osteosarcoma cells.

PTH activates multiple second messengers in its target cells, but the level at which the hormonal signal splits into different pathways is still unknown. To achieve insights on this issue, we have studied the structure-function relationship of PTH by analyzing the effects of bovine PTH-(1-34) [bPTH-(1-34)] and PTH fragments truncated at the N-terminus on the intracellular calcium concentration [( Ca2+]i) and cAMP production in the rat osteogenic sarcoma cell line UMR 106-01. [Ca2+]i was measured in single cells using fura-2. When exposed to 10(-7) M bPTH-(1-34), 20% of the cells responded with a transient increase in [Ca2+]i of variable amplitude. Equimolar doses of bPTH-(2-34), propionyl bPTH-(2-34) [(pbPTH-(2-34)], and bPTH-(3-34) also transiently increased [Ca2+]i, whereas both [tyrosine34]bPTH-(7-34) amide [bPTH-(7-34)] and bPTH-(30-34) were ineffective. The amplitude of the [Ca2+] i transients was dose-dependent, with threshold concentrations of 10(-10) M for bPTH-(1-34) and bPTH-(2-34), and 10(-9) M for bPTH-(3-34). The response rate to the active peptides ranged between 10-30%, without a clear dose-relatedness. A second addition of 10(-7) M bPTH-(1-34) to cells prestimulated with equimolar doses of bPTH-(2-34), pbPTH-(2-34), or bPTH-(3-34) produced another transient, whereas after exposure to 10(-7) M bPTH-(1-34), the cells were completely desensitized to a second homologous stimulation, suggesting that the binding affinity of the truncated peptides for the PTH receptor is lower than that of the intact bPTH-(1-34) fragment. In addition, both bPTH-(1-34) and bPTH-(2-34) dose-dependently stimulated cAMP production, but the former was more potent (ED50 = 10(-9) vs. 10(-7) M, respectively). On the contrary, pbPTH-(2-34), bPTH-(3-34), and bPTH-(7-34) had no effect on cAMP. Pretreating the cells with pertussis toxin to enhance cAMP responses via inhibition of Gi potentiated the effect of bPTH-(1-34) and bPTH-(2-34) and disclosed weak but detectable agonist action of pbPTH-(2-34). These results indicate that specific domains of the PTH molecule are linked to activation of different second messenger pathways; while the first two amino acids are indispensable for activating the cAMP system, generation of the [Ca2+]i signal appears to involve a longer domain, including the amino acid residue in position 3.

Animals↗
PubMed1991

Systemic mastocytosis presenting as osteoporosis: a clinical and histomorphometric study.

Ten patients with systemic mastocytosis (SM) were evaluated for their metabolic bone disease (4 men and 6 women; mean +/- SD, 59 +/- 13 yr). All patients presented with generalized osteopenia and/or atraumatic vertebral compression fractures. Three patients had long-standing urticaria pigmentosa; in these, the diagnosis of cutaneous mastocytosis had been established by skin biopsy. One of the 3 and 2 of the other 7 individuals had symptoms suggestive of SM. Although six patients had previously undergone decalcified bone marrow trephine core biopsy (DBMB), findings were consistent with SM in only 2 of them. X-Ray survey revealed generalized osteopenia in all 10 patients and vertebral compression fractures in 9. No patient had sclerotic bone lesions. Histological findings of undecalcified transiliac crest biopsy (UTBB) specimens from 9 patients (5 patients underwent both DBMB and UTBB, 4 underwent only UTBB, and 1 had only DBMB) disclosed bone marrow that contained nodules characteristic of mast cell granulomas and numerous scattered oval- and spindle-shaped mast cells. The trabecular bone contained abundant newly synthesized bone matrix and a significant increase in osteoblastic, osteoclastic, and resorptive surfaces. Dynamic histomorphometric parameters revealed a significantly increased mineral apposition rate. Our study suggests that SM may be a more frequent cause of osteoporosis than previously recognized. Generalized osteopenia with compression fractures may be the only presentation of SM. Undecalcified bone biopsy is useful in the diagnosis of SM. Accelerated bone remodeling is a characteristic histomorphometric feature of SM with diffuse osteopenia.

Adult↗
PubMed1991

Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass.

To define the potential role of subclinical vitamin D deficiency in postmenopausal bone loss, we analyzed the levels of circulating 25-hydroxyvitamin D (25OHD) in 539 midwestern caucasian women screened for osteoporosis. Low 25OHD (less than 38 nmol/L) was found in 49 subjects (aged 52-77 yr). Women with low 25OHD had a reduced vertebral bone density (VBD), assessed by quantitative computed tomography, compared to age-matched controls (P less than 0.001). They also had significantly lower levels of serum calcium and phosphate, lower urinary calcium, higher serum alkaline phosphatase, and, in most cases, increased immunoreactive PTH (iPTH) concentrations, suggesting secondary hyperparathyroidism. Furthermore, only in the low 25OHD group did VBD correlate directly with 25OHD (r = 0.41; P less than 0.01), and inversely with iPTH (r = -0.47; P less than 0.01). Multivariate analyses revealed that iPTH was the major determinant of the observed decrease in VBD. Seasonal variations of serum 25OHD were noted only in the control population; in this group the 25OHD levels also correlated with sunlight exposure (r = 0.48; P less than 0.01), as assessed by an outdoor score. Thus, vitamin D deficiency develops when both the endogenous and exogenous sources are insufficient and contributes to a reduced bone mass in elderly women.

Aged↗
PubMed1991

A comparison of dual energy radiography measurements at the lumbar spine and proximal femur for the diagnosis of osteoporosis.

In this study we assessed the ability of proximal femur and spine DER measurements to discriminate between control (C) and osteoporotic (OP) subjects as well as the reproducibility of the femoral DER technique. DER measurements of the proximal femur and spine (L2-L4) were obtained in 58 control (unfractured) and 54 osteoporotic (vertebral fractured) women. Linear regression analyses for each site with age suggested that density values from the Ward's triangle region explained the majority of variance due to age in the decline of bone density in both control (r = -0.45; P less than 0.0005) and osteoporotic subjects (r = 0.34; P less than 0.05), with similar findings for the femoral neck in OP subjects (r = -0.30; P less than 0.05). No other femoral site produced a significant correlation with age, and vertebral measurements were the lowest in OP subjects (r = -0.11; P = NS). Cross-sectional rates of bone loss in each region implied that for OP subjects the Ward's triangle and femoral neck regions detected the largest amount of bone loss (0.64% and 0.38%/yr, respectively), while vertebral measurements were again the smallest (0.19%/yr). Results indicated that proximal femur measurements can be obtained with relatively good precision (coefficients of variation ranged from 1.9% for femoral neck to 3.0% for Ward's triangle). Finally, receiver operating characteristic curves revealed that both Ward's triangle and femoral neck densities were able to more successfully discriminate control from osteoporotic subjects than vertebral measurements. These data support the contention that measurement of skeletal sites rich in trabecular bone, such as the femur, are more useful for diagnosing osteoporosis than DER measurements of the lumbar spine. The data also suggest that the femur may be a better site than the lumbar spine for the clinical evaluation of osteoporosis with the DER technique.

Aged↗
PubMed1990

Vertebral cortical bone mass measurement by a new quantitative computer tomography method: correlations with vertebral trabecular bone measurements.

Previous studies comparing axial and appendicular skeleton have shown that trabecular bone loss is greater than cortical bone loss. However, whether the same difference exists between the trabecular and the cortical compartments of the vertebral body remains to be determined. In this study, we used quantitative computer tomography (QCT) to simultaneously measure the cortical rim of the vertebral body as well as trabecular bone. In 99 Caucasian women (mean age 53.8 +/- 13.0 years, range 26-79 years) we found a significant correlation between cortical mineral content (BMCC) and both single (SE) and dual energy (DE) trabecular mineral content (BMCT) (r = 0.62, P less than 0.0001 for both regressions). The cross-sectional rates of bone loss per year were 1.32%, 1.16%, and 0.59% for SE-BMCT, DE-BMCT, and BMCC, respectively. BMCC decreased at a rate that was 45-51% that of SE-BMCT and DE-BMCT, respectively. Our results indicate that (1) QCT may provide a useful means to selectively measure cortical density in vertebral bodies; (2) the decrease of cortical density over time in the spine appears to have been underestimated previously by extrapolation from appendicular bone measurements; (3) because measurements of the entire vertebral body (exclusive of the posterior elements) may provide information that is more representative of spine changes with age, a measurement that includes both areas might be more useful than one measuring only the trabecular region.

Adult↗
PubMed1990

Cyclic AMP-dependent and calcium-dependent signals in parathyroid hormone function.

Previous work demonstrated that parathyroid hormone (PTH) activates the Ca2+/protein kinase C (PKC) system in addition to cAMP production. Therefore, the authors explored the role of cAMP-dependent and Ca2(+)-dependent signals in the regulation of osteoblastic growth and bone resorption. In exponentially growing UMR 106-01 osteogenic sarcoma cells, PTH (10(-7) M) inhibited [3H] thymidine incorporation by 80%. This effect was reproduced by maximal doses of both dibutyryl-cAMP (dbcAMP) and forskolin. The Ca2+ ionophore ionomycin (10(-7) M) had no effect, whereas phorbol 12-myristate 13-acetate (PMA) was slightly mitogenic. The antimitogenic action of dbcAMP was dose-dependent, with ED0.5 at about 3 X 10(-5) M. Ionomycin enhanced this dbcAMP effect at submaximal doses of the cAMP analog. PMA used in combination with both dbcAMP and ionomycin induced further depression of cell proliferation, indicating synergism with cAMP. Both dbcAMP (10(-4) M) and ionomycin (10(-7) M) stimulated 45Ca release from fetal rat limb bones after five days in culture, although the Ca2+ ionophore was less potent. 1-Oleoyl 2-acetyl-glycerol (2 X 10(-6) M) was ineffective alone, and slightly inhibited the 45Ca release produced by the other second messenger analogs in all combinations. The combination of dbcAMP and ionomycin showed a synergistic effect, and fully reproduced PTH effect. In conclusion, PTH signal transduction for control of cell proliferation and bone resorption is mediated mainly by cAMP. Activation of the Ca2+/PKC message system is nevertheless necessary to express a full hormonal response in both cell and organ culture systems.

Animals↗
PubMed1990

The role of interleukin-1 in postmenopausal bone loss.

Interleukin-1 (IL-1), a cytokine best known for its ability to stimulate lymphocyte proliferation, has recently been shown to stimulate bone resorption and modulate bone formation in vivo. Consequently, the authors have devised a series of studies to investigate the relationship between bone remodeling, menopause, and monocyte IL-1-secretion. In a first study, monocytes from osteoporotic patients were found to produce more IL-1 than monocytes from control subjects. IL-1 activity was also found to reflect histomorphometric indices of bone formation, but not of bone resorption. In a second study, devised to assess the effect of menopause on the relationship between IL-1 and bone turnover, a significant correlation was found between IL-1 and BGP in premenopausal osteoporotic women and osteoporotic men, but not in both postmenopausal osteoporotic subjects and normal subjects of either sex. In a third study, IL-1 from untreated postmenopausal women was found to be higher than in either untreated premenopausal or estrogen/progesterone-treated postmenopausal women. A significant negative correlation was found between IL-1 and years since menopause in both the healthy and osteoporotic postmenopausal women. Premenopausal IL-1 levels were achieved within eight years of menopause in the healthy but not in the osteoporotic subjects. In osteoporotic women, high IL-1 levels were evident as long as 15 years after menopause. IL-1 also correlated inversely with mineral density as measured by quantitative computer tomography. In prospective study, treatment with estrogen/progesterone caused a significant increase in IL-1 activity. This data indicates that monocyte IL-1 production mirrors the rate of bone turnover in both the healthy and osteoporotic patient, and that alteration in IL-1 production may underlie the postmenopausal acceleration of bone loss and its inhibition by ovarian steroids.

Bone Density↗
PubMed1990

Nongenomic activation of the calcium message system by vitamin D metabolites in osteoblast-like cells.

1,25-dihydroxycholecalciferol (1,25(OH)2D3) rapidly affects calcium (Ca2+) transport in several cell systems, suggesting physiological actions independent of genomic activation. To test this hypothesis, we studied immediate to early effects (0.5-300 sec) of 1,25(OH)2D3 on cytosolic Ca2+ [Ca2+]i in single osteogenic sarcoma ROS 17/2.8 cells loaded with fura-2. An acute rise in [Ca2+]i was observed in 40% of the cells following addition of 1,25(OH)2D3, with a threshold concentration of 10(-11) M. In most cases, the [Ca2+]i rise was transient, with return to baseline within 1 min; less frequently a more prolonged effect was observed, with variable recovery times. 25-hydroxycholecalciferol (25(OH)D3) reproduced the effect of 1,25(OH)2D3 on [Ca2+]i, with equal potency and similar responses, whereas 24,25-dihydroxycholecalciferol, 1 alpha-hydroxycholecalciferol, and 22 oxa-1,25(OH)2D3 were not effective. 1,25(OH)2D3 also increased [Ca2+]i in ROS 24/1 cells, which are defective of receptors for the vitamin D metabolites. At high doses (10(-8)-10(-7) M) of 1,25(OH)2D3 the [Ca2+]i rise in ROS 17/2.8 cells was due to both influx of extracellular Ca2+ and release of Ca2+ from intracellular stores, as the effect was only partially inhibited by Ca2(+)-channel blockade by nifedipine. At low doses (10(-9)-10(-10) M), the effect was entirely dependent on extracellular Ca2+. 1,25(OH)2D3 also increased the production of inositol 1,4,5 trisphosphate (Ins(1, 4, 5)P3) and diacylglycerol, at a threshold dose of 10(-9) M, indicating activation of phospholipase C (PLC). In two thirds of the cells studied, a second addition of 1,25(OH)2D3 within 5 min to cells prestimulated with equimolar doses of the vitamin D metabolite resulted in a [Ca2+]i transient of higher amplitude than the first, a phenomenon occurring at all doses of the hormone, and associated with production of Ins(1, 4, 5)P3. This response amplification was not produced by 25(OH)D3, and pretreatment with 1 alpha(OH)D3 did not significantly enhance 1,25(OH)2D3-induced production of Ins(1, 4, 5)P3. In conclusion, activation of the Ca2+ message system by vitamin D metabolites is a rapid, nongenomic effect; 1,25(OH)2D3 specifically activates both PLC and dihydropyridine-sensitive Ca2+ channels, and "primes" the cells to respond with an enhanced [Ca2+]i rise to a subsequent homologous stimulation; the presence of both the 1 alpha and 25 hydroxyl groups is necessary to express the full hormonal action of vitamin D on [Ca2+]i.

Animals↗
PubMed1990

Dual energy radiography versus quantitative computer tomography for the diagnosis of osteoporosis.

In this study we compared dual energy radiography (DER), a new, highly precise x-ray densitometric technique recently devised for measurements of vertebral mineral density and quantitative computer tomography (QCT), a densitometric technique that selectively measures the trabecular compartment of the vertebra. DER and QCT measurements were obtained in 56 healthy (H) and 48 fractured osteoporotic (OP) women using a Hologic QDR 1000 bone densitometer and a GE 9800 scanner, respectively. DER was significantly correlated with QCT in both the H (r = 0.75; P less than 0.0001) and the OP subjects (r = 0.58; P less than 0.0001). DER decreased significantly with age in the H (P less than 0.05), but not in the OP women, whereas QCT was related to age in both the H (P less than 0.0001) and the OP subjects (P less than 0.01). The rate of bone loss with age was also higher with QCT than with DER in both normal and osteoporotic women. The difference in bone density between the H and the OP subjects was larger (P less than 0.05) with QCT than with DER. Receiver operating characteristic analysis revealed that QCT was a better predictor of vertebral fractures than DER. A larger percentage of OP subjects were 2 SD or more below the normal predicted value with QCT (41%) than with DER (29%). Furthermore, the slopes of the regressions of bone density with age for normal and osteoporotic women were significantly different (P less than 0.05) with QCT but not with DER. These findings are consistent with a disproportionate loss of trabecular bone with age in osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1990

Lateral dual energy radiography: a new method for measuring vertebral bone density: a preliminary study.

Dual energy radiography (DER) is a new technique for non-invasive measurement of vertebral bone mineral density, which because of its high precision (1%), is particularly suitable for prospective analyses of time-related changes in bone mass. However, we recently found that DER is less sensitive to demineralization of trabecular bone than quantitative computed tomography (QCT). Since the compact bone of the posterior vertebral elements are included in the standard anterior-posterior DER (APDER), but not in QCT measurements, changes in trabecular bone mass attending the early phases of the osteoporotic process go undetected with the APDER technique due to the preponderance of cortical mass. Lateral-view DER (LDER), however, would minimize the contribution of vertebral compact bone as well as intra-abdominal calcifications to the trabecular component. To determine the in vivo short-term precision of the LDER method, we obtained three measurements in 18 healthy women, aged 23 to 76, during a four-week period. In addition, both APDER and LDER measurements were obtained in 53 healthy women, aged 23 to 80. The coefficient of variation for LDER was 2.8%. LDER density values accounted for a higher percentage of the variance of bone mass measurements with age (47%) than APDER (23%). Moreover, LDER declined significantly with age in both premenopausal (r = -0.42, p less than 0.05) and post-menopausal women (r = -0.50, p less than 0.005), whereas the age-related changes in APDER values failed to reach statistical significance in either group. The rate of bone loss with age in the premenopausal group was 0.45% per year with LDER, and 0.10% per year with APDER. Postmenopausal women showed a 0.78% loss of bone mass per year with LDER and 0.47% per year with APDER. The correlation between APDER and LDER was significant (r = 0.78, p less than 0.01). The accumulated data indicate that LDER may be a more appropriate technique than APDER for detecting the initial loss of vertebral trabecular bone that characterizes early subclinical osteoporotic syndrome.

Adult↗
PubMed1990

Increased monocyte interleukin-1 activity and decreased vertebral bone density in patients with fasting idiopathic hypercalciuria.

Idiopathic hypercalciuria (IH) is a heterogeneous disorder frequently observed in patients with nephrolithiasis. At one extreme of its clinical spectrum is fasting hypercalciuria (FH), a condition characterized by increased bone resorption and turnover. In previous studies we have shown that monocytes from patients with high turnover osteoporosis and from women in early postmenopause elaborate increased amounts of interleukin-1 (IL-1), a cytokine that stimulates bone resorption in vitro and in vivo. Since IL-1 could also mediate the resorptive mechanism of FH and cause a clinically significant bone loss, we have studied the relationship of IH, vertebral mineral density, bone turnover, and monocyte IL-1 activity in 47 patients with absorptive hypercalciuria (AH), 23 with FH, and 38 nonhypercalciuric subjects with recurrent nephrolithiasis (controls). Vertebral mineral density, as measured by quantitative computer tomography, was decreased in each of the three patient groups, but was significantly lower in FH patients than in AH patients or control subjects. Twenty-four-hour total urinary hydroxyproline excretion was increased in FH patients compared to that in AH patients or controls, but blood levels of osteocalcin were not. Monocytes from FH subjects yielded significantly more IL-1 (alpha + beta) activity than those from AH patients or controls; levels of IL-1 activity in monocytes of AH and control patients were similar. In IH subjects, significant correlations were found between IL-1 and hydroxyproline (r = 0.70; P less than 0.0001), IL-1 and quantitative computer tomography values (r = -0.49; P less than 0.005), and IL-1 and urinary calcium (r = -0.36; P less than 0.05). Serum PTH levels were within normal limits in all subjects and were similar in the three study groups, 1,25-Dihydroxyvitamin D3 levels, although higher in IH patients than in controls, were not significantly different in FH and AH subjects. Increased IL-1 activity and decreased vertebral mineral density are features of a subset of patients with IH. Although a cause-effect relationship remains to be established, increased monocytic IL-1 activity, rather than elevated PTH or 1,25-dihydroxyvitamin D3 levels, could underlie the resorptive component of FH.

Adult↗
PubMed1989

Osteoporotic bone fragility. Detection by ultrasound transmission velocity.

We evaluated ultrasound transmission velocity at the patella as an indicator of osteoporotic fragility in 293 nonobese women. Osteoporosis was defined by atraumatic vertebral compression deformity. Ultrasound velocity averaged 1954 +/- 71 (+/- SD) m/s in premenopausal normal women and declined significantly with age after menopause, largely independently of age-related loss of spine bone mass. Postmenopausal osteoporotic women had lower velocities than normal women (-76 m/s). After allowing for slight differences in age between the groups, the difference (-54 m/s) was still significant. Women with velocities below 1825 m/s were about six times more likely to have one or more fractures than women with velocities about that level. By sensitivity-specificity analysis, ultrasound velocity discriminated between normal and osteoporotic women as well as direct measurement of spine bone mass. Ultrasound velocity measures both bone mass and a component of bone fragility distinct from decreased mass; it is a potentially valuable new tool for evaluating women for osteoporotic fragility.

Adult↗
PubMed1989

Effect of L-lysine on cytosolic calcium homeostasis in cultured human normal fibroblasts.

L-lysine, a cationic essential amino acid, has been reported to affect calcium transport in both intestine and kidney. In order to investigate whether this effect is associated with changes in cytosolic calcium homeostasis, we studied the effect of L-lysine deprivation on intracellular calcium concentration ([Ca2+]i), as well as 45Ca efflux and accumulation in normal human fibroblasts. Steady state [Ca2+]i, measured using fura-2 fluorescence in cells cultured for 18 hours in a L-lysine-free medium, was significantly higher than in cells grown in the presence of as little as 4 microM L-lysine. L-lysine deprivation also led to a significant decrease of 45Ca fractional efflux compared with cells grown in complete medium. This effect was paralleled by a significant decrease in 45Ca accumulation. Lack of L-arginine from the growth medium for the same time period had no effect on either [Ca2+]i, 45Ca efflux, or 45Ca accumulation rate. Presumably, the lack of L-lysine for a significant amount of time impairs the active mechanisms of calcium extrusion, which is only partially compensated by a reduction of calcium accumulation rate. This leads to an increased steady state [Ca2+]i. It is concluded that L-lysine is an important modulator of cytosolic calcium homeostasis.

Calcium↗
PubMed1989

Abnormal cell calcium concentrations in cultured bone cells obtained from femurs of obese and noninsulin-dependent diabetic rats.

Cytoplasmic free calcium concentration [Ca2+]i was quantified in cultured bone cells with osteoblastic characteristics. The cells were obtained from femurs of obese (fa/fa) Wistar-Kyoto rats, from nonobese, noninsulin-dependent diabetic (NIDD) Sprague Dawley rats, and from their appropriate controls. [Ca2+]i was also determined in bone cells obtained from in vivo insulin-treated NIDD rats. Obese (Wistar Kyoto) rats had increased body weight (313 +/- 13 vs. 249 +/- 4 g; P less than 0.01), decreased femur weights (0.68 +/- 0.05 vs. 0.89 +/- 0.05 g; P less than 0.05), similar glucose levels (148 +/- 5 vs. 139 +/- 3 mg/dl), and higher plasma insulin levels (6.0 +/- 0.5 vs. 0.7 +/- 0.1 ng/ml; P less than 0.01) when compared with their nonobese [(fa/+); (+/+)] littermates. Nonobese, NIDD rats, compared with their appropriate controls (nondiabetic Sprague Dawley rats) had higher plasma glucose levels (235 +/- 32 vs. 145 +/- 3 mg/dl; P less than 0.01) but their plasma insulins, body weights, and femur weights were similar to controls (0.7 +/- 0.1 vs. 0.6 +/- 0.1 ng/ml; 302 +/- 4 vs. 318 +/- 14 g; 0.97 +/- 0.4 vs. 0.98 +/- 0.04 g, respectively). Long-term (4 weeks) daily insulin treatment (2 u/100 g) of the NIDD rats increased their plasma insulin (1.9 ng/ml; P less than 0.05) and body weight (369 +/- 13 g; P less than 0.05) but did not change their plasma glucose levels (225 +/- 5 mg/dl), or femur weights (0.98 +/- 0.4 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗