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PubMed1999

Expression of polysialylated NCAM but not L1 or N-cadherin by regenerating adult mouse optic fibers in vitro.

This study asks if there might be irreversible maturational changes in adult neurons that limit their capacity to regenerate. Retina from adult and embryonic mouse were placed in culture on laminin substrates so that regenerating adult optic fibers could be compared to growing embryonic fibers. Several cell adhesion molecules (CAMs) known to mediate the growth of embryonic neurites on astrocytes were assayed by immunocytochemistry: L1, N-cadherin, and NCAM. Thy 1.2, a potential CAM with inhibitory activity, was also examined. As in vivo, embryonic fibers were found to express both L1 and N-cadherin. In contrast, regenerating adult fibers had no detectable amounts of either of these CAMs. N-Cadherin is normally down regulated during development so its absence in adult fibers suggests it can not be reexpressed during regeneration. L1 is normally found in the proximal regions of adult optic fibers so its absence indicates it is not expressed or transported in regenerating fibers. Adult regenerating fibers expressed high levels of Thy 1.2, which was undetectable in embryonic optic fibers. Thy 1.2 is normally found in mature fibers, indicating this phenotypic feature is preserved during regeneration. Both adult and embryonic fibers showed strong reactivity for NCAM, which in vivo is normally found in embryonic and at lower levels in adult fibers. Surprisingly, both embryonic and regenerating adult fibers expressed high levels of polysialic acid, which is normally absent in adult fibers. NCAM may be one of few CAMs available to adult optic fibers for regeneration on astrocytes.

Animals↗
PubMed1995

Axonal regeneration into chronically denervated distal stump. 1. Electron microscope studies.

In this study, we have analyzed the ability of axons to regenerate into chronically denervated peripheral nerve. As an experimental rat model, the proximal end of a newly transected rat tibial nerve was sutured into chronically denervated (3 months up to 16 months) common peroneal nerve. Samples for morphological studies were collected 3 and 6 weeks after anastomosis of the tibial and common peroneal nerves. Our results showing a distinct organization of the endoneurial matrix in the chronically denervated distal stumps conformed with those from previous studies. Long cytoplasmic processes of endoneurial fibroblasts in close contact with collagen fibrils (with a diameter of 50-60 nm) surrounded areas of thin collagen fibrils (with a diameter of 25-30 nm). Remnants of Schwann cell columns (i.e., bands of Büngner) were situated in areas of thin collagen fibrils. After 12 months of denervation the majority of the Schwann cells columns were replaced by thin collagen fibrils. Successful axonal regeneration was noted in distal stumps that had been denervated for 14 and even 16 months. However, axonal regeneration diminished with prolonged denervation. The regenerating axons grew through the areas of thin collagen fibrils. The maturation and thickening of the regenerated axonal sprouts resulted in a decrease in areas of thin collagen fibrils. These results suggest that a chronically denervated nerve stump has the capacity to meet regenerating axons even after 16 months of denervation, although the progressive atrophy of Schwann cell columns impairs the likelihood of good axonal regeneration. The areas of thin collagen fibrils may act as a 'plastic' bed for successful axonal regeneration, and a study of these fibrils may provide further insight into the role of the extracellular matrix during peripheral nerve regeneration.

Anastomosis, Surgical↗
PubMed1995

Myelinated nerve fibre regeneration in diabetic sensory polyneuropathy: correlation with type of diabetes.

Observations were made on myelinated fibre regeneration in diabetic sensory polyneuropathy assessed in sural nerve biopsy specimens. These confirmed that regenerative clusters initially develop within abnormally persistent Schwann cell basal laminal tubes. The number of regenerating fibres, identified by light microscopy, was found to decline in proportion to the reduction in total myelinated fibre density. The relative number of regenerating fibres was significantly greater in patients with insulin-dependent as compared with those with non-insulin-dependent diabetes after correction for age. There was a slight negative correlation between the relative proportion of regenerating fibres and age, but this was not statistically significant. The progressive reduction in the number of regenerating fibres with declining total fibre density indicates that axonal regeneration fails with advancing neuropathy. The production of nerve growth factor (NGF) and NGF receptors by denervated Schwann cells is likely to be important for axonal regeneration. To investigate whether the failure of axonal regeneration could be related to a lack of NGF receptor production by Schwann cells, we examined the expression of p75 NGF receptors by Büngner bands immunocytochemically. In comparison with other types of peripheral neuropathy, p75 NGF receptor expression appeared to take place normally. It is concluded that failure of axonal regeneration constitutes an important component in diabetic neuropathy. Its explanation requires further investigation.

Adult↗
PubMed1989

Muscle regeneration. The effect of hypophysectomy on cell proliferation and expression of insulin-like growth factor-I.

Against the background of the importance of growth hormone (GH) for normal muscle growth, a study was performed to investigate whether lack of GH after hypophysectomy affects the cell proliferation and the local production of insulin-like growth factor-I (IGF-I) in the early stages of muscle regeneration in adult rats. The level of IGF-I in the serum of hypophysectomised rats was reduced to about 30% of that of controls. The incorporation of [methyl-3H]thymidine into the regenerating muscle showed a peak 6 days after the operation and then gradually declined to the end of the period of study 30 days after initiation of regeneration by ischemic necrosis. The DNA content rose to a maximum level after 6-8 days, and remained high after 30 days. There was no major difference in the incorporation of [3H]thymidine in regenerating muscle of hypophysectomised and control rats, but the DNA concentration in the regenerating muscles of hypophysectomised rats was significantly reduced after 30 days. There was a corresponding reduction in the number of nuclei per muscle fibre, indicating that hypophysectomy has a small effect on the cell proliferation during the early stages of muscle regeneration. Immunohistochemical demonstration of IGF-I in the regenerating muscle revealed the transient presence of immunoreactive material in satellite cells and myotubes after 6 to 8 days of regeneration but no immunoreactivity after 30 days. No obvious difference was observed between hypophysectomised and control rats, indicating that the endogenous production of IGF-I in regenerating skeletal muscle can occur independently of GH.

Animals↗
PubMed2004

Quantitative trait loci affecting plant regeneration from protoplasts of Brassica oleracea.

Quantitative trait loci (QTLs) controlling the plant-regeneration ability of Brassica oleracea protoplasts were mapped in a population of 128 F(2) plants derived from a cross between the high-responding, rapid-cycling line and a low-responding, broccoli breeding line of B. oleracea. A modified bulked segregant analysis with AFLP markers identified two QTLs for plant regeneration. In a multiple regression analysis, the two QTLs explained 83% of the total genetic variation for regeneration recorded 15 weeks after initial transfer of microcalli to regeneration medium. Both QTLs showed additive effects, and the alleles contributing to the high regeneration frequencies were derived from the high-responding, rapid-cycling line. Using microsatellites with known location, the two QTLs were mapped to linkage groups O2 and O9 on the map published by Sebastian et al. [(2000) Theor Appl Genet 100:75-81] or to chromosomes C8 and C7 on the map published by Saal et al. [(2001) Theor Appl Genet 102:695-699]. QTLs for the early flowering trait of the rapid-cycling parent have previously been mapped to the same two linkage groups. Association between flowering time and regeneration ability was, however, not found in the present material, indicating that plant-regeneration ability can be transferred between cultivars independently of the early flowering trait. The detection of two major QTLs for plant regeneration in B. oleracea may provide the initial step towards the identification of markers suitable for marker-assisted selection of regeneration ability.

Brassica↗
PubMed2003

Globulin-1 gene expression in regenerable Zea mays (maize) callus.

Since maize callus cultures regenerate plants via somatic embryogenesis, one might expect to find similar proteins in both zygotic embryos and tissue cultures. The 63-kD globulin protein designated GLB1, the expression of which is regulated by abscisic acid (ABA), is one such protein. When maize Type I regenerable callus was exposed for 24 h to 0.1 m M ABA or a water stress induced by 0.53 M mannitol, GLB1 was produced as determined by Western analysis. This protein was not detected in ABA or mannitol-treated regenerable cultured tissue of a null genotype or in tissues not exposed to ABA or water stress. Exposure to ABA in the culture medium increased the callus ABA levels greatly but a mannitol-induced water stress had only a small effect on ABA levels. Regenerable callus exposed to 0.1 m M ABA also produced mRNA that hybridized on a Northern blot with a globulin- 1 gene ( Glb1) probe. When both Type I and Type II regenerable cultured tissues were exposed to regeneration medium without ABA or mannitol, several GLB1 antibody immunoreactive proteins were produced. These proteins were not detected in regenerated plants nor in non-regenerable callus treated with ABA. These results suggest that: (1) at least for expression of Glb1, somatic embryogenesis is similar to zygotic embryogenesis, (2) there may be a regulatory role for auxin in the processing of Glb1-encoded polypeptides since fewer are seen when dicamba is present in the medium, (3) ABA has a role in somatic embryogenesis, and (4) regenerability of a maize callus culture may be assessed by treating the cultured tissue with 0.1 m M ABA to determine if GLB1 proteins are induced.

Abscisic Acid↗
PubMed2003

Regeneration of flax ( Linum usitatissimum L.) plants from anther culture and somatic tissue with increased resistance to Fusarium oxysporum.

The aim of this study was to establish a protocol for the efficient production of flax plants of microspore origin. The results were compared to those obtained for plants regenerated from somatic explants from hypocotyls, cotyledons, leaves, stems and roots. All the plants obtained during the experiments were regenerated from callus that was grown for periods from a few weeks to a few months before the regeneration was achieved. Anther cultures were less effective in plant regeneration than somatic cell cultures. However, regenerants derived from anther cells showed valuable breeding features, including increased resistance to fungal wilt. The age of the donor plants and the season they grew in had a noticeable effect on their anther callusing and subsequent plant regeneration. Low temperature had a negative effect and dark pre-treatment a positive effect on callusing and plant regeneration. Different media were most effective for callus induction, shoot induction and rooting. For callus induction two carbon sources (2.5% sucrose and 2.5% glucose) were most effective; for shoots, only sucrose at lower concentration (2%) was effective. Rooting was most efficient in 1% sucrose and reduced (50%) mineral concentration in the medium. It was found that the length of in vitro cultivation significantly increases the ploidy and affects such features as regenerant morphological characteristics, petal colour, and resistance to Fusarium oxysporum-induced fungal wilt. The established plant regeneration system provides a basis for the creation of transgenic flax.

Culture Techniques↗
PubMed2003

Induced androgenesis in tomato (Lycopersicon esculentum Mill.). III. Characterization of the regenerants.

We present data on the morphological, cytological, biochemical and genetic characteristics of tomato regenerants obtained through anther culture. As a result of induced androgenesis, more than 6,000 rooted regenerants were developed that differed both from the donor plants and among each other with respect to habitus and leaf, flower and inflorescence morphology. Cytological analysis revealed a great variability in chromosome number in the cells of the regenerated plants. While most of the regenerants were mixoploid, the majority of the cells had a haploid chromosome number. R(1) and R(2) progenies were tested for their resistance to Clavibacter michiganense subsp. michiganense ( Cmm 7). Some of the regenerants were resistant to the pathogen. A biochemical analysis of fruit from R(3) and R(4) plants showed a higher content of dry matter, sugars and vitamin C in the regenerant plants obtained from the hybrids than in those from the cultivars and control plants. The values of the parameters of hybrid regenerants grown in the greenhouse were about 1.5-fold higher than those of the hybrid regenerants grown in the field, and this trend is clearly expressed in all of the hybrid regenerants. The results obtained suggest that induced androgenesis and gametoclonal variation may be used as an additional tool to create a large range of new forms. The application of the latter in breeding programs would accelerate the development of tomato lines and varieties that would be more productive, disease-resistant, highly nutritive and flavour-acceptable.

Actinomycetales↗
PubMed2003

Sugarbeet (Beta vulgaris L.): shoot regeneration from callus and callus protoplasts.

The successful application of recombinant DNA technology for crop plants requires efficient regeneration systems. A detailed study on the regeneration potential of callus and callus-derived protoplasts of a recalcitrant species, sugarbeet, was performed. A reproducible and highly efficient method for induction of regenerable friable callus was established from etiolated hypocotyl explants. A reduced sucrose concentration proved beneficial. Successful shoot regeneration could be demonstrated in 10 out of 12 tested lines. Seed germination, followed by callus induction and shoot regeneration required only a single culture medium. Additionally, the regeneration capacity of roots and root-derived callus was demonstrated. Highly efficient plant regeneration was also achieved when using protoplasts isolated from regenerable friable callus induced on etiolated hypocotyls explants. To our knowledge this represents the first report on callus protoplast to plant regeneration in sugarbeet.

Beta vulgaris↗
PubMed2004

Growth and apoptosis during larval forelimb development and adult forelimb regeneration in the newt ( Notophthalmus viridescens).

Many of the genes involved in the initial development of the limb in higher vertebrates are also expressed during regeneration of the limb in urodeles such as Notophthalmus viridescens. These similarities have led researchers to conclude that the regeneration process is a recapitulation of development, and that patterning of the regenerate mimics pattern formation in development. However, the developing limb and the regenerating limb do not look similar. In developing urodele forelimbs, digits appear sequentially as outgrowths from the limb palette. In regeneration, all the digits appear at once. In this work, we address the issue of whether regeneration and development are similar by examining growth and apoptosis patterns. In contrast to higher vertebrates, forelimb development in the newt, N. viridescens, does not use interdigital apoptosis as the method of digit separation. During adult forelimb regeneration, apoptosis seems to play an important role in wound healing and again during cartilage to bone turnover in the advanced digits and radius/ulna. However, similar to forelimb development, demarcation of the digits in adult forelimb regeneration does not involve interdigital apoptosis. Outgrowth, rather than regression of the interdigital mesenchyme, leads to the individualization of forelimb digits in both newt development and regeneration.

Animals↗
PubMed1998

Cellular and molecular mechanisms of arm regeneration in crinoid echinoderms: the potential of arm explants.

Crinoid echinoderms can provide a valuable experimental model for studying all aspects of regenerative processes from molecular to macroscopic level. Recently we carried out a detailed study into the overall process of arm regeneration in the crinoid Antedon mediterranea and provided an interpretation of its basic mechanisms. However, the problem of the subsequent fate of the amputated arm segment (explant) once isolated from the animal body and of its possible regenerative potential have never been investigated before. The arm explant in fact represents a simplified and controlled regenerating system which may be very useful in regeneration experiments by providing a valuable test of our hypotheses in terms of mechanisms and processes. In the present study we carried out a comprehensive analysis of double-amputated arm explants (i.e. explants reamputated at their distal end immediately after the first proximal amputation) subjected to the same experimental conditions as the regenerating donor animals. Our results showed that the explants undergo similar regenerative processes but with some significant differences to those mechanisms described for normal regenerating arms. For example, whilst the proximal-distal axis of arm growth is maintained, there are differences in terms of the recruitment of cells which contribute to the regenerating tissue. As with normal regenerating arms, the present work focuses on (1) timing and modality of regeneration in the explant; (2) proliferation, migration and contribution of undifferentiated and/or dedifferentiated/transdifferentiated cells; (3) putative role of neural growth factors. These problems were addressed by employing a combination of conventional microscopy and immunocytochemistry. Comparison between arm explants and regenerating arms of normal donor adults indicates an extraordinary potential and regenerative autonomy of crinoid tissues and the cellular plasticity of the phenomenon.

Animals↗
PubMed2006

Identification of key tissue type for antler regeneration through pedicle periosteum deletion.

Epimorphic regeneration is the "holy grail" of regenerative medicine. Research aimed at investigating the various models of epimorphic regeneration is essential if a fundamental understanding of the factors underpinning this process are to be established. Deer antlers are the only mammalian appendages that are subject to an annual cycle of epimorphic regeneration. In our previous studies, we have reported that histogenesis of antler regeneration relies on cells resident within the pedicle periosteum (PP). The present study elaborates this finding by means of functional studies involving the deletion of PP. Four yearling and four 2-year-old stags were selected for total PP deletion or partial PP deletion experiments. Of the animals in the total PP deletion group, one showed no signs of antler regeneration throughout the antler growth season. Two showed substantial and one showed marginal delays in antler regeneration (at 34, 20 and 7 days, respectively) compared with the corresponding sham-operated sides. Histological investigation revealed that the delayed antlers were derived from regenerated PP. Unexpectedly, the regenerative capacity of the antler from the total periosteum-deleted pedicles depended on antler length at surgery. Of the four deer that had partial PP deletion, two regenerated antlers exclusively from the left-over PP on the pedicle shafts in the absence of participation from the pedicle bone proper. The combined results from the PP deletion experiments convincingly demonstrate that the cells of the PP are responsible for antler regeneration.

Animals↗
PubMed1997

Expression of basic fibroblast growth factor-like immunoreactivity in the nuclei of regenerating hepatocytes.

This study, utilizing rats subjected to two-thirds partial hepatectomy or sham operation, was designed (1) to investigate the content of basic fibroblast growth factor (bFGF) in the subcellular fractions of regenerating and sham-operated rat livers by immunoblot experiments and enzyme-linked immunosorbent assay (ELISA), (2) to show that bFGF immunoreactivity and proliferating cell nuclear antigen (PCNA) immunoreactivity are markers for hepatocellular mitosis before and after partial hepatectomy, and (3) to observe the location and fine structure of the bFGF immunoreaction within the regenerating liver with special attention to bFGF immunoreactivity in the nuclei of regenerating hepatocytes. Immunoblot experiments and ELISA showed a transient increase in high-molecular-weight forms of bFGF in the nuclear subcellular fraction of regenerating liver 48 h after partial hepatectomy. By light microscopy, bFGF and PCNA immunoreactivities were detected in the nuclei of regenerating hepatocytes. Electron microscopy demonstrated bFGF-like immunoreactivity mainly in the nuclear euchromatin and rarely in the heterochromatin or nucleoli of regenerating hepatocytes. The transient increase in high-molecular-weight forms of bFGF in the nuclear euchromatin of regenerating hepatocytes, together with the concomitant expression of PCNA in the regenerating liver, suggests an important role of the high-molecular-weight forms of bFGF in hepatocyte proliferation and/or mitosis, although authentic bFGF with a molecular form of 18 kDa is not considered to be involved in hepatic regeneration.

Animals↗
PubMed2004

Molecular and clinical basis for the regeneration of human gastrointestinal epithelia.

In the gastrointestinal tract, rapid renewal of the epithelium continues throughout life. Therefore, it is believed that the gastrointestinal epithelium has a prominent capacity for regeneration when tissue damage occurs. However, we face some clinical conditions in which regeneration of the gastrointestinal epithelia is severely disturbed. One example is the refractory ulcers seen in the intestine of inflammatory bowel disease patients, and a novel therapy to regenerate damaged intestinal epithelia is earnestly desired in those conditions. Little is known about the maintenance and regeneration of the intestinal epithelia, and a molecular or clinical basis for regenerative medicine is totally lacking at the moment. In this review, we discuss recent findings of the molecules regulating the proliferation and differentiation of epithelial cells. Further study of these molecules may lead to the identification and purification of intestinal stem cells that may be used as a source for transplantation in diseased patients. Endogenous stem cells also could be manipulated to correct dysregulated or prolonged regeneration in diseased patients. Alternatively, we will raise bone marrow cells as another novel source for regenerating the intestinal epithelia. Bone marrow-derived cells are the only cells of extragastrointestinal origin that are shown to contribute to the regeneration of the gastrointestinal epithelia. In bone marrow transplant recipients, donor-derived epithelial cells substantially repopulated the gastrointestinal tract during epithelial regeneration after graft-versus-host disease or ulcer formation. Utilization of these cells may also lead to a novel therapy to regenerate the damaged gastrointestinal epithelia, whether by bone marrow transplantation or by the administration of humoral factors.

Animals↗
PubMed2005

Differential expression of genes at stages when regeneration can and cannot occur after injury to immature mammalian spinal cord.

Comprehensive screens were made for genes that change their expression during a brief critical period in development when neonatal mammalian central nervous system (CNS) loses its capacity to regenerate. In newly born opossums older than 12 days regeneration ceases to occur in the cervical spinal cord. It continues for 5 more days in lumbar regions. The mRNA's expressed in cords that do and do not regenerate were analyzed by polymerase chain reaction-based subtractive hybridization. The mRNAs extracted from cervical cords of animals aged 9 and 12 days were subtracted reciprocally, old from young and young from old. Additional subtractions were made between lumbar regions of 12 day-old cords (which can regenerate) and cervical regions (which cannot). Mini libraries of approximately 2000 opossum cDNA clones resulted from each subtraction. Many sequences were novel. Others that were expressed differentially were related to cell growth, proliferation, differentiation, motility, adhesion, cytoskeleton and extracellular matrix. A major task was to narrow the search and to eliminate genes that were not associated with regeneration. Clones from different subtractions were cross-hybridized. After those common to regenerating and nonregenerating cords were rejected, approximately 284 sequences of interest remained. Our results revealed novel sequences, as well as genes involved in transcription, cell signaling, myelin formation, growth cone motility, liver regeneration, and nucleic acid and protein management as the candidates important for neuroregeneration. For selected genes of potential interest for regeneration (for example cadherin, catenin, myelin basic protein), their temporal and spatial distributions and levels of expression in the CNS were measured by Northern blots, semiquantitative and real-time RT-PCR, and in situ hybridization. Our experiments set the stage for testing the efficacy of candidate genes in turning on or off the capacity for spinal cord regeneration. Opossum spinal cords in vitro provide a reliable and rapid assay for axon outgrowth and synapse formation.

Animals↗
PubMed1992

Regulation by thyroid hormone of the synthesis of a cytosolic thyroid hormone binding protein during liver regeneration.

To understand the regulation by thyroid hormone, 3,3',5-triiodo-L-thyronine (T3), of the synthesis of a cytosolic thyroid hormone binding protein (p58-M2) during liver regeneration, the synthesis of p58-M2 was evaluated. The synthesis of p58-M2 was measured by metabolic labeling of primary cultures derived from the regenerating liver of euthyroid, hypo- or hyperthyroid rats. During regeneration, the increase in the liver/body weight ratio is approximately 25% higher in hyper- than in hypothyroid rats. However, T3 has no effect on the rate of overall liver regeneration observed in four days. In mature liver, T3 increased the synthesis of p58-M2 by approximately 2.5-fold. During regeneration, however, the change in the synthesis of p58-M2 varied with the thyroid status. In euthyroid rats, the synthesis of p58-M2 continued to increase up to 2-fold during liver regeneration. In hyperthyroid rats, after an initial increase by 1.5-fold on day 1, the synthesis of p58-M2 subsequently declined during regeneration. In hypothyroid rats, the synthesis of p58-M2 remained virtually unchanged during regeneration. These results indicate that T3 regulates the synthesis of p58-M2 in mature and regenerating liver.

Animals↗
PubMed1988

Influence of non-neuronal cells on regeneration of the rat sciatic nerve.

The ability of the rat sciatic nerve to regenerate into a previously frozen distal nerve segment was studied and compared to regeneration after a crush lesion. The regeneration rate in the frozen segment was 1.9 mm/day, which was approximately half of that observed after a crush lesion (3.3 mm/day). If an unfrozen nerve segment was left intact beyond the frozen section, the rate of regeneration increased to 3.2 mm/day. However, a fresh nerve segment sutured along the frozen segment did not significantly affect the rate of regeneration. Incorporation of [3H]thymidine in the regenerating nerve, analyzed after 1, 3 and 6 days, showed an increased labelling in the frozen segment. This increase spread from the proximal nerve segment into the frozen section. In nerves where a segment was left intact beyond the frozen section, [3H]thymidine incorporation was seen to enter the frozen section from both sides. The spreading of [3H]thymidine incorporation appeared to correlate with the rate of regeneration. However, the same pattern of incorporation could be observed in nerves where regeneration was detained by a transection. The results suggest that Schwann and/or other cells which invade the frozen nerve segment affect the rate of axonal elongation, and that the migration of these cells occurs independently of regenerating fibers.

Animals↗
PubMed1989

Nerve regeneration and serum levels of insulin-like growth factor-I in rats with streptozotocin-induced insulin deficiency.

Peripheral nerve regeneration was studied in female Sprague-Dawley rats with streptozotocin-induced insulin deficiency. Nerve regeneration was provoked by a crush lesion on the sciatic nerve 21 days after the streptozotocin injection. The regeneration was assessed by a pinch test at different time-points after injury. The rate of regeneration in insulin-deficient animals, 2.5 mm/day, was significantly lower than in control animals, 2.9 mm/day (P less than 0.05). There was no difference in the initial delay, i.e. the period before regeneration attains a constant velocity. One group of insulin-deficient rats was treated with insulin during the regeneration period by means of implanted osmotic mini-pumps. This treatment prevented the decrease in regeneration. After 6 days the sciatic nerves of insulin-deficient rats had regenerated 12.3 +/- 0.3 mm (mean +/- S.E.M.), while the corresponding value for insulin-treated rats was 15.7 +/- 0.6 mm. (P less than 0.01). The streptozotocin-treated rats were found to have a 39% reduction in the serum level of insulin-like growth factor-I (IGF-I) compared to control rats (0.33 +/- 0.02 micrograms/ml and 0.54 +/- 0.02 micrograms/ml respectively, P less than 0.001). Insulin treatment during the regeneration period completely restored the IGF-I level back to normal.

Animals↗