Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “secretion defect”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed1991

Normal sequence of the gonadotropin-releasing hormone gene in patients with idiopathic hypogonadotropic hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) results from absent or greatly diminished secretion of GnRH. Defects in the GnRH gene have been identified in an animal model of IHH and have been hypothesized as a possible basis for GnRH deficiency in humans. In this study, we used the polymerase chain reaction to clone and sequence the coding regions, promoter, and 3' untranslated tract of the GnRH genes from both alleles of four unrelated patients with IHH. One of the patients studied is a member of a kindred in which X-linked inheritance has been excluded by father-to-son transmission of the disease. No DNA sequence mutations were found. We conclude that most cases of IHH in humans do not involve mutations in the GnRH gene and are presumably caused by mutations at one or more other genetic loci that are required for normal function of GnRH-producing neurons.

Adolescent↗
PubMed2002

Mechanisms in the development of type 2 diabetes mellitus.

The leading cause of death among patients with type 2 diabetes mellitus (DM) is cardiovascular disease, with 75% of these deaths attributed to coronary heart disease. Over the previous two decades the pathophysiological basis of type 2 DM has been extensively investigated. Although many of the underlying molecular mechanisms involved in the development of this disorder remain to be explained, it is clear that type 2 DM is a complex medical disorder characterized by insulin resistance and defects in insulin secretion. The process through which the metabolic derangements of type 2 DM accelerate the development of cardiovascular disease in type 2 DM has yet to be determined and remains an area of intense investigation, focusing on hyperglycemia and insulin resistance as major underlying contributors. This article explores current information related to the pathophysiology of type 2 DM alone and its relationship to the development to cardiovascular disease.

Coronary Disease↗
PubMed2001

Effects of therapy with lansoprazole on intestinal permeability and inflammation in young cystic fibrosis patients.

BACKGROUND: Defective pancreatic bicarbonate secretion with low intestinal pH or intestinal inflammation of any origin increase intestinal permeability in cystic fibrosis (CF). METHODS: In this open study, the authors evaluated the effect of a proton-pump inhibitor on intestinal permeability and inflammation in 14 young, pancreatic-insufficient CF patients. Permeability was measured by a three-sugar permeability test before and after 1 year of lansoprazole use, and urinary nitric oxide (NO) oxidation products were assessed before and during that year as a marker of inflammation. RESULTS: After 1 year of lansoprazole use, median urinary recovery percentages changed from 2.5% to 1.7% (P = 0.064), from 24.9% to 24.5% (no significance), and from 10.5% to 11.1% (no significance) for lactulose, mannitol, and L-rhamnose, respectively. Despite the fact that the median urinary excretion ratios decreased from 0.108 to 0.083 (P = 0.03) and from 0.246 to 0.176 (P = 0.016) for lactulose and mannitol and for lactulose and rhamnose, respectively, they both remained increased. Median urinary NO products-to-creatinine ratios were 0.287 for CF patients before lansoprazole and 0.130 for healthy control participants (P = 0.002). Although there was a tendency toward a decrease in the NO products-to-creatinine ratio during treatment, this was not significant at the end point. CONCLUSIONS: Intestinal permeability is considerably increased in CF patients and is partly corrected after the use of a proton-pump inhibitor for 1 year, which may point to a harmful effect of the acid luminal contents on the tight junctional related paracellular permeability pathway. The start and end values for the NO products-to-creatinine ratio in CF patients were not significantly different, but were considerably increased when compared with control participants (P = 0.002).

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Bone defect repair with tissue-engineered cartilage.

We tested the efficacy of a new approach for the tissue-engineered growth of cartilage developed in our laboratory in repairing surgically created bone defects in the craniums of rats. Large cranial defects were created bilaterally in the frontoparietotemporal bones of athymic nude rats (n = 10). There was gross evidence of new cartilage in 8 of 10 experimental defects that had been filled with a synthetic biocompatible, biodegradable polymer template that had been seeded in vitro with freshly isolated chondrocytes. The control defects, filled with either nothing at all or a polymer template without chondrocytes, showed no evidence of cartilaginous repair (0 of 10). Statistical analysis using McNemar's test with pooled samples showed significant differences between the two groups (p < 0.05). Prior reports concerning the biologic repair of bony defects involved stimulation of adjacent mesenchymal tissue and resulted in ingrowth of new bone. To our knowledge, this is the first report of structural cartilaginous repair of a bony defect with matrix secreted by implanted chondrocytes.

Animals↗
PubMed1991

Abnormal B-cell function in rats with non-insulin-dependent diabetes induced by neonatal streptozotocin: effect of in vivo insulin, phlorizin, or vanadate treatments.

Neonatal rats treated with streptozotocin on day 5 after birth (n5-STZ model) exhibited, when fully grown, a frank basal hyperglycemia (17.4 +/- 0.7 vs. 6.6 +/- 0.2 mmol/L in nondiabetic rats), a specific failure of glucose-induced insulin release, and hyperresponse to arginine. To investigate whether or not chronic correction of the hyperglycemia can improve the defects on insulin secretion, we tested diverse maneuvers, all of which aimed to lower chronically the hyperglycemia. Insulin secretion was studied with the isolated perfused pancreas preparation. A 16-day subcutaneous insulin therapy (approximately 10 U/kg/day) unevenly correcting the plasma glucose levels (10.8 +/- 1.6 mmol/L) did not improve the lack of insulin response to glucose while the arginine-induced insulin release returned to values close to normal. A 28-day intraperitoneal phlorizin infusion (50 mg/kg/day0 or a 20-day oral vanadate administration (40 mg/kg/day) caused near normalization of the basal plasma glucose level in the treated n5-STZ rats (7.8 +/- 0.5 and 8.2 +/- 0.5 mmol/L, respectively). Nevertheless, these treatments did not correct the insulin secretion in response to glucose nor the hyperresponsiveness to arginine. Furthermore, we investigated whether or not glucopenia in vitro could restore the glucose-induced insulin release in this diabetic model. After a 50 min glucose-free period, the insulin response to a subsequent glucose stimulation still did not materialize. These observations suggest that in the present n5-STZ diabetic model, (a) hyperresponsiveness to arginine cannot be solely regarded as a residual effect of hyperglycemia; (b) the return to normal values of insulin release in response to arginine after insulin therapy, despite a still prevailing mild hyperglycemia, suggests that exogenous insulin per se may regulate to some extent the diabetic B cells; and (c) near normalization of the basal glucose levels is not a sufficient condition to obtain improvement of the B-cell response to glucose, such a finding being consistent with the concept that stringent normalization of glycemia is a prerequisite.

Animals↗
PubMed1992

Insulin resistance and insulin deficiency in the pathogenesis of posttransplantation diabetes in man.

Although steroids can induce insulin resistance, it is not known whether additional defects in insulin secretion are necessary for the development of diabetes. To address this question, we measured insulin sensitivity (euglycemic insulin clamp in combination with indirect calorimetry and infusion of tritiated glucose) and insulin secretion (hyperglycemic clamp) in three groups of subjects: (1) 10 kidney transplant patients with normal oral glucose tolerance, (2) 14 patients who developed diabetes after kidney transplantation, and (3) 10 healthy controls. Glucose utilization, primarily storage of glucose as glycogen, was reduced by 34% in kidney transplant patients with normal glucose tolerance when compared with healthy control subjects (18.2 +/- 2.9 vs. 27.5 +/- 2.7 microM/L; P less than 0.05). Insulin secretion was normal in relation to the degree of insulin resistance in transplanted non-diabetic patients, thus maintaining a normal oral glucose tolerance. Development of transplantation diabetes was associated with only minor further deterioration of glucose storage (14.7 +/- 2.7 microM/L; P less than 0.001 vs. control subjects), whereas first-phase, second-phase, and glucagon-stimulated insulin secretion measured during hyperglycemic clamping (incremental area under the insulin curve 287 +/- 120, 1275 +/- 419, and 3515 +/- 922 pM) became impaired as compared with nondiabetic kidney transplant patients (769 +/- 216, 3084 +/- 545, and 6293 +/- 533 pM; P less than 0.05). We conclude that both insulin resistance and insulin deficiency are necessary for the development of diabetes in kidney transplant patients.

Adult↗
PubMed1994

Maturity-onset diabetes of the young.

Maturity-onset diabetes of the young (MODY) is an autosomal dominant-subtype of noninsulin-dependent diabetes mellitus, characterized by an early age of onset. MODY is considered a model for genetic studies of noninsulin-dependent diabetes mellitus because of the availability of large multigenerational families, which make linkage analyses possible. So far, two MODY susceptibility loci have been reported, one unknown gene on chromosome 20q, and glucokinase on chromosome 7q. Glucokinase mutations appear to be the most common cause of MODY in the European population, being found in 60% of the families investigated. This form of diabetes results from a primary defect in insulin secretion due to the reduced enzymatic activity of the mutant glucokinase. The search for a third MODY gene will provide a better understanding of diabetes in childhood.

Age of Onset↗
PubMed1997

Antral and fundic D-cell numbers in Helicobacter pylori infection.

OBJECTIVES: Helicobacter pylori infection is associated with an exaggeration of gastrin release following meals or bombesin stimulation attributed to a defect of somatostatin secretion of antral D-cells. Nevertheless, these modifications of gastric physiology do not explain the increase of gastric acid secretion which is only observed in duodenal ulcer patients. The inhibitory effect of somatostatin secretion of fundic D-cells on parietal cells is well known. The aim of our prospective study was to compare the number of fundic D-cells and likewise the number of antral G-cells and D-cells between patients with duodenal ulcer and healthy subjects with and without H. pylori infection. METHODS: The numbers of D-cells and G-cells were compared between 19 infected patients with duodenal ulcer and 20 healthy subjects, 10 with and 10 without H. pylori infection. Fundic mucosal biopsy specimens were examined using immunohistochemical techniques specific for the presence of somatostatin, antral mucosal biopsy specimens for the presence of gastrin and somatostatin. RESULTS: The number of G-cells was significantly lower (P = 0.0012) in duodenal ulcer patients by comparison with infected subjects and controls. The number of antral D-cells was significantly less (P < 0.0001) in duodenal ulcer patients (mean of 10 random fields = 0.45 +/- 0.04) than in either asymptomatic infected patients (0.65 +/- 0.07) or uninfected controls (0.88 +/- 0.10). The number of fundic D-cells was significantly lower (P < 0.0001) in duodenal ulcer patients (mean = 0.20 +/- 0.03) than in either asymptomatic infected subjects (0.29 +/- 0.05) or controls (0.73 +/- 0.09); here the difference between the two groups of infected subjects was not significant. Multivariate analysis showed that the presence of H. pylori infection of the fundic mucosa did not influence the number of fundic D-cells. CONCLUSION: Changes in the number of fundic and antral D-cells induced by H. pylori infection did not explain abnormalities of gastric acid secretion usually observed in duodenal ulcer patients; it is suggested that pre-existing abnormalities in the regulation of parietal cell or increase of parietal cell mass are involved.

Adult↗
PubMed1984

Corticotrophin releasing factor: responses in normal subjects and patients with disorders of the hypothalamus and pituitary.

Synthetic CRF-41 has been given to 43 patients with hypothalamic, pituitary or adrenal diseases and contrasted with the responses in 20 normal subjects. In the normal subjects the mean increment in serum cortisol (+/- SE) was 276 +/- 38 nmol/l; the increments showed a significant negative correlation with the basal serum cortisol levels (r = -0.56; P less than 0.02). The mean peak serum cortisol was 662 +/- 34 nmol/l and the mean peak corticosterone was 28.6 +/- 3.8 nmol/l. There was a significant positive correlation between the peak serum corticosterone and cortisol concentrations (r = 0.84; P less than 0.0001). Dexamethasone pretreatment abolished the rise in cortisol in response to CRF-41. The peak serum cortisol following CRF-41 was not significantly different between the normal subjects and those patients with pituitary disease who had normal cortisol responses to insulin-induced hypoglycaemia. However, in individual patients the peak cortisol levels induced by hypoglycaemia were greater than, but significantly correlated with, those induced by 100 micrograms of CRF-41. Seven patients were ACTH deficient in response to hypoglycaemia, and of these six responded normally to CRF-41. Only one of these patients had a lesion clearly originating in the hypothalamus; four had pituitary tumours with suprasellar extensions and the remaining patient had idiopathic GH and ACTH deficiency. Our data suggest that these patients have a functional defect of ACTH secretion due to the failure of CRF to reach the corticotroph. Of the four patients with pituitary-dependent Cushing's disease who were on no treatment at the time of testing, three showed an exaggerated and one a normal response to CRF-41. These normal or enhanced responses of hypercortisolaemic patients with Cushing's syndrome contrast with the complete inhibition of the responses to CRF-41 in normal subjects given dexamethasone. In the treated patients with Cushing's syndrome and normal serum cortisol levels, those with pituitary-dependent disease showed an enhanced ACTH response to CRF-41 as compared with the ectopic ACTH group, but there was some overlap between the two groups. Acromegalic patients did not show a GH response to CRF-41. We conclude that administration of CRF-41 is a safe new method for investigating disorders of the hypothalamo-pituitary axis.

Acromegaly↗
PubMed1995

Understanding the pathogenesis of type 2 diabetes: can we get off the metabolic merry-go-rounds?

The aetiology of non-insulin-dependent diabetes mellitus (NIDDM) is not known. The concordance of NIDDM in identical twins and differences in the prevalence rate of NIDDM between different racial groups suggest a genetic cause. Hyperglycaemia in established diabetes is caused by a combination of hepatic insulin resistance, impaired peripheral (muscle and fat) glucose uptake and a defect in glucose-mediated insulin secretion. However, it is not known if these defects are all inherited or if one can cause the others. This uncertainty is due to the fact that hyperglycaemia per se can cause defects in insulin action and insulin secretion that resemble those found in NIDDM. Furthermore the elevated free fatty acid (FFA) levels found when NIDDM is associated with obesity are known to cause both peripheral and hepatic insulin resistance. Recently we have demonstrated the mechanism by which elevated FFA levels can cause hepatic insulin resistance. However, we also have evidence that the converse holds in that genetically engineered hepatic insulin resistance in a transgenic rat model leads to obesity. Thus an understanding of the pathogenesis of NIDDM is complicated by the fact that hyperglycaemia and obesity can be both causes and consequences of insulin resistance. To overcome these difficulties, studies in young euglycaemic diabetes-prone subjects have been conducted. Results suggest that there may be different causes for NIDDM in different racial groups.

Animals↗
PubMed1997

Fluid transport across cultures of human tracheal glands is altered in cystic fibrosis.

1. There is evidence that defective submucosal gland secretion contributes to the airway pathology of cystic fibrosis (CF). Using a capacitance probe technique, we have compared fluid transport across submucosal gland cultures from individuals with and without CF. 2. Under baseline conditions, approximately 60% of non-CF cultures secreted fluid; the rest absorbed. In secreting tissues, amiloride increased secretion, whereas in absorbing tissues it reduced or reversed absorption. 5-Nitro-2(3-phenylpropylamino)-benzoate (NPPB) a blocker of the CF transmembrane conductance regulator (CFTR), converted secretion to absorption. Thus, the direction and magnitude of baseline fluid movement depended on a balance between active absorption of Na+ and cAMP-dependent secretion of Cl-. 3. 8-(4-Chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT-cAMP), methacholine and luminal uridine 5'-triphosphate (UTP) all induced or increased fluid secretion across non-CF cultures. Results with NPPB and with 4,4'-diisothiocyanatostilbene-2,2'-disulphonate (DIDS), a blocker of Ca(2+)-activated Cl- channels, suggested that fluid secretion induced by CPT-cAMP was mediated primarily by CFTR; UTP acted entirely via Ca(2+)-activated Cl- channels, and methacholine activated both pathways. 4. All CF cultures showed baseline fluid absorption, which was abolished by amiloride. 5. CF cultures showed a normal secretory response to UTP, a reduced response to methacholine, and no response to CPT-cAMP. 6. Thus, the absorptive processes of airway glands are retained in CF, but the cAMP-dependent secretory process is lost. This would markedly reduce the water content of gland secretions. The resulting change in viscosity would contribute to the accumulation of airway mucus which is characteristic of this disease.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMedDate not supplied

Ichthyosis associated with ARC syndrome: ARC syndrome is one of the differential diagnoses of ichthyosis.

The arthrogryposis, renal tubular dysfunction and cholestasis syndrome is rare. Novel identification of the mutation in VPS33B in this syndrome, which involves intracellular protein trafficking by regulation of vesicle-to-target sensory nerve action potential receptor (SNARE) family, might explain the consistent combination of membrane fusion defects. We can guess the defective lamellar body secretion mediated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor or SNARE protein pathway in the epidermis might result in the ichthyosiform phenotype. In the English-language literature, half of the reported instances of this syndrome are associated with ichthyosis. We report an infant with ichthyosis in association with arthrogryposis, renal tubular dysfunction, and cholestasis syndrome, and review the literature. Our findings suggest that the differential diagnosis of ichthyosis during infancy should include this syndrome.

Abnormalities, Multiple↗
PubMed1998

Neuroendocrine dysfunction in African trypanosomiasis. The role of cytokines.

Sleeping sickness (SS; African trypanosomiasis) is an anthropozoonosis transmitted by the tsetse fly. Infection with Trypanosoma brucei in humans is associated with adynamia, lethargy, anorexia, and more specifically amenorrhea/infertility in women and loss of libido/impotence in men. Recent evidence suggests that experimental infection in animals with Trypanosoma brucei species causes polyglandular endocrine failure by local inflammation of the pituitary, thyroid, adrenal, and gonadal glands. In a cross-sectional study we investigated the prevalence and significance of neuroendocrine abnormalities in 137 Ugandan patients with SS. In the untreated stage of the disease, there was a high prevalence of adrenal insufficiency (27%), hypothyroidism (50%) and hypogonadism (85%). Pituitary function tests suggested an unusual combined central (hypothalamic/pituitary) and peripheral defect in hormone secretion. Specific therapy resulted in a rapid recovery of adrenal/thyroid function, whereas hypogonadism persisted for years in a substantial portion of patients. We did not detect pituitary, thyroid, adrenal, and gonadal autoantibodies in patients with endocrine dysfunction, ruling out an autoimmune origin of the endocrine abnormalities. However, the presence of hypopituitarism correlated with high cytokine concentrations (TNF-alpha, IL-6) which--together with direct parasitic infiltration of the endocrine glands--are involved in the pathogenesis of SS-associated endocrine dysfunction.

Animals↗
PubMed1983

Alkaline phosphatase secretion-negative mutant of Bacillus licheniformis 749/C.

An alkaline phosphatase secretion-blocked mutant of Bacillus licheniformis 749/C was isolated. This mutant had defects in the phoP and phoR regions of the chromosome. The selection procedure was based on the rationale that N-methyl-N'-nitro-N-nitrosoguanidine can induce mutations of closely linked multiple genes. The malate gene and the phoP and phoR genes are located at the 260-min position in the Bacillus subtilis chromosome; hence, the malate gene could be used as a marker for the mutation of the phoP and phoR regions of the chromosome. In a two-step selection procedure, strains defective in malate utilization were first selected with the cephalosporin C procedure. Second, these malate-defective strains were further screened in a dye medium to select strains with defects in alkaline phosphatase secretion. One stable mutant (B. licheniformis 749/cNM 105) had a total secretion block for alkaline phosphatase and had the following additional characteristics: (i) the amount of alkaline phosphatase synthesized was comparable to that in the wild type; (ii) the alkaline phosphatase was membrane bound; (iii) the mutant strain alkaline phosphatase, in contrast to that of the wild type, could not be extracted with MgCl2, although the amounts of protein extracted from each strain were comparable; (iv) the sodium dodecyl sulfate-polyacrylamide gel pattern of MgCl2-extracted proteins from the mutant strain was different from that of the wild-type proteins; (v) the mutant, unlike the wild type, could not use malate as a sole source of carbon; and (vi) the outside surface of the wall of the mutant cells contained an additional electron-dense layer that was not present on the wild-type cell wall surface.

Alkaline Phosphatase↗
PubMed1987

Lipoprotein nature of the colicin A lysis protein: effect of amino acid substitutions at the site of modification and processing.

The colicin A lysis protein (Cal) is required for the release of colicin A to the medium by producing bacteria. This protein is produced in a precursor form that contains a cysteine at the cleavage site (-Leu-Ala-Ala-Cys). The precursor must be modified by the addition of lipid before it can be processed. The maturation is prevented by globomycin, an inhibitor of signal peptidase II. Using oligonucleotide-directed mutagenesis, the alanine and cystein residues in the -1 and +1 positions of the cleavage site were replaced by proline and threonine residues, respectively, in two different constructs. Both substitutions prevented the normal modification and cleavage of the protein. The marked activation of the outer membrane detergent-resistant phospholipase A observed with wild-type Cal was not observed with the Cal mutants. Both Cal mutants were also defective for the secretion of colicin A. In one mutant, the signal peptide appeared to be cleaved off by an alternative pathway involving signal peptidase I. Electron microscope studies with immunogold labeling of colicin A on cryosections of pldA and cal mutant cells indicated that the colicin remains in the cytoplasm and is not transferred to the periplasmic space. These results demonstrate that Cal must be modified and processed to activate the detergent-resistant phospholipase A and to promote release of colicin A.

Amino Acid Sequence↗
PubMed1995

Growth hormone deficiency and empty sella in DIDMOAD syndrome: an endocrine study.

Two girls with DIDMOAD syndrome are presented. One also had severe megaloblastic-sideroblastic anaemia and the other several neurological manifestations. Both were short with defective growth hormone secretion. Computed tomography revealed empty sella in both girls; one had widespread atrophic cortical and cerebellar changes. High doses of thiamine improved the anaemia in the first case, increased C peptide secretion in both, but had no effect on the neurological abnormalities.

Anemia, Sideroblastic↗
PubMed2005

Monogenic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and beta cell failure.

Type 2 diabetes mellitus is caused by a combination of insulin resistance and beta cell failure. The polygenic nature of type 2 diabetes has made it difficult to study. Although many candidate genes for this condition have been suggested, in most cases association studies have been equivocal. Monogenic forms of diabetes have now been studied extensively, and the genetic basis of many of these syndromes has been elucidated, leading to greater understanding of the functions of the genes involved. Common variations in the genes causing monogenic disorders have been associated with susceptibility to type 2 diabetes in several populations and explain some of the linkage seen in genome-wide scans. Monogenic disorders are also helpful in understanding both normal and disordered glucose and insulin metabolism. Three main areas of defect contribute to diabetes: defects in insulin signalling leading to insulin resistance; defects of insulin secretion leading to hypoinsulinaemia; and apoptosis leading to decreased beta cell mass. These three pathological pathways are reviewed, focusing on rare genetic syndromes which have diabetes as a prominent feature. Apoptosis seems to be a final common pathway in both type 1 and type 2 diabetes. Study of rare forms of diabetes may help ion determining new therapeutic targets to preserve or increase beta cell mass and function.

Animals↗
PubMed1996

New treatments for patients with type 2 diabetes mellitus.

In subjects with type 2 diabetes, both defects of insulin secretion and insulin resistance contribute to the development of hyperglycaemia. The major goals of treatment are to optimise blood glucose control, and normalise the associated lipid disturbances and elevated blood pressure. Pharmacologic treatment is often necessary. This paper discusses new forms of oral treatment for subjects with type 2 diabetes. These include a new sulphonylurea compound glimepiride (Amaryl), which binds to a different protein of the putative sulphonylurea receptor than glibenclamide, and seems to have a lower risk of hypoglycaemia. A new class of drugs with insulin secretory capacity, of which repaglinide (NovoNorm) is the leading compound, is now in phase III clinical trials. Alpha-glucosidase inhibitors reversibly inhibit alpha-glucosidase enzymes in the small intestine, which delays cleavage of oligo- and disaccharides to monosaccharides. This leads to a delayed and reduced blood glucose rise after a meal. Two compounds are in development or have been marketed, ie, miglitol and acarbose (Glucobay). Another new class of drugs is the thiazolidine-diones, which seem to work by enhancing insulin action. The 'insulin sensitising' effects of the leading compounds, troglitazone and BRL 49653C, do not involve any effect on insulin secretion. These drugs also seem to beneficially influence serum cholesterol and triglyceride levels. Oral antihyperglycaemic agents can be used only during a limited period of time in most patients, after which the diabetic state 'worsens' and insulin therapy has to be started. In this light, two new forms of treatment which require subcutaneous injections are also discussed: the synthetic human amylin analogue AC137 (pramlintide) and glucagon-like peptide-1 (7-36)-amide, a strong glucose-dependent stimulator of insulin secretion. It remains to be seen whether these compounds can be developed further for clinical use in patients with diabetes.

Amyloid↗