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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To define glucose flux in a state of chronic endogenous insulin excess, a patient with an insulinoma was studied. Plasma glucose, insulin (IRI), glucagon (IRG) and glucose turnover ([3-3H]glucose infusion) were measured before and after insulinoma resection in the postabsorptive state (PA), during a glucose infusion adjusted to attain euglycemia (before insulinoma resection only) and following an intravenous glucagon bolus (1 mg). Before insulinoma resection, plasma glucose was 55 mg/dl, glucose production (Ra) and disappearance (Rd) were equal (1.6 mg/kg/min) and glucose clearance was elevated (2.8 ml/kg/min) in PA. When glycemia was raised with a glucose infusion to 77 mg/dl, Rd did not change; in contrast Ra dropped to zero. Plasma IRI and IRG concentrations were 0.7 ng/ml and 110 pg/ml respectively before glucose infusion and remained constant throughout. After resection of the insulinoma, glycemia in PA was 103 mg/dl, Ra and Rd were increased slightly to 1.9 mg/kg/min while the metabolic clearance of glucose was decreased by 25% (2.1 ml/kg/min). Glucagon stimulation pre- and postinsulinoma resection resulted in significant increases in glycemia and IRI. We conclude that hypoglycemia with insulinoma is a consequence of decreased glucose production and increased glucose clearance. Hepatic sensitivity to small increments in glycemia is markedly enhanced so as to fully suppress endogenous glucose production at euglycemic levels in the absence of any change in IRI and IRG. The mechanisms controlling hepatic Ra in insulinoma appear different from normal.
Diabetes Res Clin Pract
PMID:Glucose turnover in insulinoma--a case report. 303 48

Glucagon may play a role in the metabolic derangements of overt Type 2 (non-insulin-dependent) diabetes mellitus. We therefore have evaluated the early steps in glucagon action by investigating the hormone-sensitive adenylyl cyclase system in liver membranes from seven Type 2 diabetic patients with fasting hyperglycaemia and two-fold elevations in plasma glucagon. The comparison was made with seven control subjects matched for age, sex and body weight. Glucagon receptor binding was almost identical in the two groups. There were, however, marked alterations in the adenylyl cyclase activity in membranes from the diabetic patients. This activity was reduced by 35-50% when compared to control activity. Basal cyclase activity, as well as the activity after stimulation with glucagon or with agents (i.e., sodium fluoride and forskolin) that act beyond the glucagon receptor, was significantly decreased (p less than 0.05, p less than 0.001 respectively). In conclusion, uncontrolled Type 2 diabetes in associated with an over-all loss of responsiveness of the hormone-sensitive adenylyl cyclase in human liver, which apparently results from post-receptor alterations. This change may provide a mechanism for reducing the effect of hyperglycagonaemia in Type 2 diabetes mellitus.
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PMID:Altered action of glucagon on human liver in type 2 (non-insulin-dependent) diabetes mellitus. 303 42

Basal, postprandial (2 h after breakfast), and glucagon-stimulated plasma C-peptide concentrations were determined in a group of 36 adult diabetic patients. Basal and postprandial C-peptide values were measured on consecutive days to estimate the degree of variation of C-peptide secretion. In a subgroup of 15 diabetic patients treated chronically with diet and oral hypoglycemic agents (sulfonylureas or a combination of sulfonylureas and metformin), we studied whether administration of sulfonylureas immediately before breakfast had any effect on postprandial C-peptide values. Absolute differences between two consecutive fasting C-peptide concentrations in insulin-requiring patients were less than 0.1 nM in all but 1 patient, in whom the difference was 0.18 nM. In subjects treated with oral hypoglycemic agents the median difference was 0.12 nM (range 0-0.38 nM). Absolute differences between two consecutive postprandial C-peptide concentrations were all less than 0.1 nM in insulin-requiring patients. No significant difference was found between postprandial C-peptide concentrations with or without preceding administration of oral hypoglycemic agents (medians 1.35 and 1.30 nM, respectively). Glucagon-stimulated C-peptide concentrations were somewhat higher than the postprandial values. However, equal discrimination between insulin-requiring and non-insulin-requiring diabetic patients was found by measuring postprandial or glucagon-stimulated C-peptide concentrations.
Diabetes Care 1988 Apr
PMID:Glucagon-stimulated and postprandial plasma C-peptide values as measures of insulin secretory capacity. 304 7

Twelve normal subjects and 10 subjects with non-insulin-dependent diabetes mellitus were given, in random order at intervals of greater than or equal to 1 wk, three drinks of the same beverage: one unsweetened, one sweetened with 400 mg aspartame, and one sweetened with 135 mg saccharin. The amount of sweetener approximated that in 1 L of sugar-free soft drink. Plasma glucose, insulin, and glucagon were measured for 3 h after ingestion of the test beverage. Plasma glucose declined slightly throughout the test period, probably due to fasting, with no differences between the three treatments. Neither sweetener affected peak insulin levels in subjects with or without diabetes. Analysis of area under the curve showed that mean insulin levels were statistically significantly higher after aspartame than after saccharin or unsweetened beverage in normal subjects only, but the magnitude of the difference was small and unlikely to be of physiological importance in the absence of differences in glucose levels. Furthermore, the differences could largely be accounted for by a decrease in insulin values after both unsweetened beverage and saccharin, with no change from baseline after aspartame. Glucagon levels showed time-to-time variation but no overall differences. We conclude that ingestion of aspartame- or saccharin-sweetened beverages by fasting subjects, with or without diabetes, did not affect blood glucose homeostasis.
Diabetes Care 1988 Mar
PMID:Response to single dose of aspartame or saccharin by NIDDM patients. 304 54

Increases in renal blood flow and glomerular filtration rate occur following the ingestion of a protein-rich meal. It has been postulated that this renal response is stimulated by some hormonal factor. Glucagon has been proposed as a probable mediating hormone, but results of recent studies argue against a direct mediating effect of glucagon. It is postulated that glomerular hyperfiltration induced by various stimuli (protein ingestion, amino acid infusion, glucagon infusion, diabetes mellitus) is associated with increased secretion by the liver of a factor that increases glomerular filtration rate. Preliminary data suggest that serotonin might play a role in mediating the postprandial increases in renal hemodynamics following protein ingestion.
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PMID:Potential role of a liver-derived factor in mediating renal response to protein. 305 8

To assess the role of counterregulatory hormones per se in the response to continuous insulin infusion, overnight-fasted dogs were given 5 mU.kg-1.min-1 insulin intraportally either alone (INS, n = 5), with glucose to maintain euglycemia (INS + GLU, n = 5), or with glucose and hormone replacement [i.e., glucagon, epinephrine, norepinephrine, and cortisol infusions (INS + GLU + HR, n = 6)]. The increases in counterregulatory hormones that occurred during insulin-induced hypoglycemia were simulated in the latter group. In this way, it was possible to separate the effects of hypoglycemia per se from those due to the associated counterregulatory hormone response. Glycogenolysis and gluconeogenesis were measured with a combination of tracer ([ 3-3H]glucose and [U-14C]alanine) and hepatic arteriovenous (AV) difference techniques during a 40-min control and a 180-min experimental period. Insulin levels increased similarly in all groups (to congruent to 250 microU/ml), whereas plasma glucose levels decreased in INS (115 +/- 3 to 41 +/- 3 mg/dl; P less than .05) and rose slightly in both INS + GLU (108 +/- 2 to 115 +/- 4 mg/dl; P less than .05) and INS + GLU + HR (111 +/- 3 to 120 +/- 3 mg/dl; P less than .05) due to glucose infusion. Glucagon, epinephrine, norepinephrine, and cortisol were replaced in INS + GLU + HR so that the increments in their levels were 102 +/- 6, 106 +/- 14, 117 +/- 9, and 124 +/- 37%, respectively, of their increments in INS. At no time was there a significant difference between the hormone levels in INS and INS + GLU + HR. The rise in the counterregulatory hormones per se accounted for only half (53 +/- 9% by the AV difference method and 54 +/- 10% by tracer method) of the glucose production associated with hypoglycemia resulting from insulin infusion. The rate and efficiency of alanine conversion to glucose in the hormone-replacement studies were only 29 +/- 10 and 50 +/- 27% of what occurred during hypoglycemia induced by insulin infusion. In conclusion, the counterregulatory hormones alone (i.e., without accompanying hypoglycemia) can account for only 50% of the glucose production that is present during insulin-induced hypoglycemia. The remaining 50%, therefore, must result from effects of hypoglycemia other than its ability to trigger hormone release.
Diabetes 1988 Nov
PMID:Stimulation of glucose production through hormone secretion and other mechanisms during insulin-induced hypoglycemia. 305 2

The effects of recombinant human growth hormone (GH, 1 micrograms/ml) and insulin-like growth factor I (IGF-I, 200 ng/ml) on the production of insulin and glucagon by human fetal islet-like cell clusters (ICCs) were studied in tissue culture. ICCs were derived after collagenase digestion and culture of pancreases from 16 fetuses (mean gestational age 15.6 wk). The ICCs were cultured with or without GH or IGF-I for 7 or 31 days. Basal rates of insulin and glucagon production were not altered by GH during the first 17 days of culture, but the release of both hormones was increasingly augmented by GH during the last 2 wk of culture (131% increase in insulin and 85% in glucagon compared with controls). ICCs cultured for 7 days in the presence of GH secreted more insulin when incubated for 120 min in 20 mM than in 2 mM glucose (2.1-fold response, P less than .05), whereas ICCs maintained in basal medium did not respond to glucose. GH had no effect on DNA and insulin content or insulin biosynthesis. Exogenous IGF-I caused a 28% suppression of insulin release (P less than .05) between days 4 and 10 of culture but induced a 49% increase in the mean secretion rate during the last week (days 25-31, P less than .01). Glucagon release was not affected by exogenous IGF-I. In contrast to GH, exogenous IGF-I induced a twofold increase in the DNA content of the 7-day--cultured ICCs. However, insulin biosynthesis and release were markedly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Dec
PMID:Effects of growth hormone and insulin-like growth factor I on endocrine function of human fetal islet-like cell clusters during long-term tissue culture. 305 61

To investigate plasma glucagon counterregulatory responses to hypoglycemia, an intravenous insulin bolus was given over 2 min to 73 children, aged 8.5-18.8 yr, with diabetes duration 1.2-17.1 yr. The plasma glucagon responses of the 61 children without glucagon antibodies or abnormal glucagon molecules were compared with those of 13 nondiabetic control subjects, aged 8.3-18.3 yr. Glucagon increments from baseline (73 +/- 10 pg/ml) and peak glucagon responses (212 +/- 13 pg/ml) were markedly lower in diabetic patients than in control subjects (341 +/- 49 and 462 +/- 51 pg/ml, respectively, P less than .001). Glucagon responses were found to correlate positively with the age of the patients at the time of testing (r = .478, P less than .001) and inversely with metabolic control as measured by glycosylated hemoglobin (r = -.342, P less than .02). There was no relationship between glucagon responses and diabetes duration. There was also no relationship between the glucagon increments and free-insulin levels during the test. Glucose recovery from the nadir was impaired in diabetic subjects compared with control subjects and correlated inversely with free-insulin levels. However, glucose recovery did not correlate with the rise of plasma glucagon. Glucose recovery was not different in patients with glucagon antibodies. In this study, we have demonstrated a deficient glucagon response to hypoglycemia in children with insulin-dependent diabetes mellitus. However, the clinical significance of this deficit is not clear.
Diabetes Care 1988 Sep
PMID:Glucagon responses to hypoglycemia in children and adolescents with IDDM. 306 2

Secretion of insulin and glucagon from perfused BB rat pancreas was examined in rats (5 weeks old; n = 6) before and 2 weeks after (13 weeks old; n = 5) the onset of diabetes mellitus. The secretion of insulin and glucagon was modified by increasing concentrations of glucose in the perfusate from 2.8 mM to 16.5 mM. In 5-week-old BB rats, glucagon secretion was higher at the low glucose concentration (2.8 mM) and insulin secretion lower at the high glucose concentration (16.5 mM) than the corresponding values in age-matched control rats. In 13-week-old BB rats, insulin secretion was undetectable irrespective of glucose concentration. Glucagon secretion was only moderately suppressed by the perfusion of high glucose (16.5 mM) and was significantly higher than that of age-matched controls. The reduction in insulin secretion observed in 5-week-old rats without insulitis indicated that pancreatic B cells of BB rats of this age are somehow injured by humoral factors rather than cell infiltration. Cell function was apparently modified indirectly by the destruction of neighboring B cells.
Diabetes Res Clin Pract 1988 Sep 05
PMID:Alteration of insulin and glucagon secretion from the perfused BB rat pancreas before and after the onset of diabetes. 306 18

Glucagon-like peptide-1 (GLP-1) (1-37) and the fraction derived from it, GLP-1 (7-36 amide), are peptides encoded by the preproglucagon gene and possibly co-secreted with enteroglucagon. When added at a 25-nM concentration, GLP-1 (7-36 amide) decreased the release of glucagon from the perfused rat pancreas from 68.5 +/- 9.0 pg/ml to 41.5 +/- 11.5 pg/ml at 2 min in the presence of 11.2 mM glucose (P less than 0.01), and from 196.0 +/- 32.5 pg/ml to 87.0 +/- 23.5 pg/ml at 5 min in the presence of 2.8 mM glucose (P less than 0.05). Insulin levels increased from 12.6 +/- 3.0 microU/ml to 48.9 +/- 14.0 microU/ml at 10 min in the presence of 11.2 mM glucose (P less than 0.05) and from 2.0 +/- 0.4 microU/ml to 8.2 +/- 2.3 microU/ml at 2 min in the presence of 2.8 mM glucose (P less than 0.05). Glucagon and insulin release were not affected significantly by GLP-1 (1-37), irrespective of glucose concentration. We suggest that GLP-1 (7-36 amide) rather than enteroglucagon may be the true physiologic gut hormone and that it may act as 'incretin' in the enteroinsular axis. We suggest further that the glucagonostatic and insulinotropic activities of this peptide are unique and might be important in islet-cell function.
Diabetes Res Clin Pract 1988 Oct 14
PMID:Glucagon-like peptide-1 (7-36 amide): a potent glucagonostatic and insulinotropic hormone. 306 10


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