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Biomedical subjects

S Efendic

Publications and source records attributed to S Efendic.

At least 163 records · Page 9Linked to original sources
PubMed1989

Glucose intolerance in uremic patients: the relative contributions of impaired beta-cell function and insulin resistance.

Glucose tolerance and tissue sensitivity to insulin were examined in 19 renal failure patients on chronic regular hemodialysis (group U) and in 6 matched control subjects with normal renal function (group A). Based on glucose tolerance as assessed by an oral glucose tolerance test (OGTT), glucose tolerance was normal in 5 (group U:N), borderline in 5 (group U:BL) and decreased in 9 uremic subjects (group U:D). Compared with group A the uremics demonstrated significantly (p less than 0.01) impaired insulin sensitivity as assessed by a continuous mixed infusion of somatostatin, insulin and glucose (SIGIT). In addition 19 non-diabetic subjects with normal fasting blood glucose and normal renal function, matching the uremic patients with respect to glucose tolerance as assessed by OGTT, were studied (group B). In group B impairments in both insulin secretion and insulin sensitivity tended to be more pronounced in subjects with decreased OGTT as compared with those with borderline OGTT. In contrast, insulin resistance was present to a similar degree in uremic subjects of group U:N, U:BL and U:D. During SIGIT endogenous insulin, glucagon and growth hormone (GH) were suppressed in both uremic and control subjects. This implies that insulin resistance in uremia is most likely not due to hyperglucagonemia or abnormal GH metabolism. During OGTT subjects of group U:N had significantly higher insulin response than subjects of group U:BL (p less than 0.02) and group U:D (p less than 0.01). Insulinogenic index was significantly higher in group U:N than in group U:BL (p less than 0.02) and group U:D (p = 0.01) and was higher in group U:BL than in group U:D (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Cholecystokinin (CCK)-33 stimulates insulin secretion from the perfused rat pancreas: studies on the structure-activity relationship.

Cholecystokinin (CCK)-33 is known to stimulate insulin secretion. Presently, using the perfused rat pancreas, we have characterized the active site in the CCK-33 molecule that is responsible for this effect by the use of different CCK fragments. We found that CCK-33, CCK-8 and CCK-7 (1 nM) all significantly stimulated insulin secretion in the presence of 4.4 mM or 6.7 mM glucose. However, CCK-7 was much less potent than the longer forms. In contrast, CCK-4, CCK-6 and CCK-33 (1-21) had no effect on insulin secretion. We conclude that the shortest CCK-form that stimulates insulin secretion at 1 nM is the C-terminal heptapeptide CCK-7. However, CCK-8 is much more potent than CCK-7 in this respect.

Animals↗
PubMed1988

Mild type II diabetes markedly increases glucose cycling in the postabsorptive state and during glucose infusion irrespective of obesity.

Glucose cycling (GC; G in equilibrium G6P) equals 14% of glucose production in postabsorptive man. Our aim was to determine glucose cycling in six lean and six overweight mild type II diabetics (fasting glycemia: 139 +/- 10 and 152 +/- 7 mg/dl), in postabsorptive state (PA) and during glucose infusion (2 mg/kg per min). 14 control subjects were weight and age matched. GC is a function of the enzyme that catalyzes the reaction opposite the net flux and is the difference between hepatic total glucose output (HTGO) (2-[3H]glucose) and hepatic glucose production (HGP) (6-[3H]-glucose). Postabsorptively, GC is a function of glucokinase. With glucose infusion the flux is reversed (net glucose uptake), and GC is a function of glucose 6-phosphatase. In PA, GC was increased by 100% in lean (from 0.25 +/- 0.07 to 0.43 +/- .08 mg/kg per min) and obese (from 0.22 +/- 0.05 to 0.50 +/- 0.07) diabetics. HGP and HTGO increased in lean and obese diabetics by 41 and 33%. Glucose infusion suppressed apparent phosphatase activity and gluconeogenesis much less in diabetics than controls, resulting in marked enhancement (400%) in HTGO and HGP, GC remained increased by 100%. Although the absolute responses of C-peptide and insulin were comparable to those of control subjects, they were inappropriate for hyperglycemia. Peripheral insulin resistance relates to decreased metabolic glucose clearance (MCR) and inadequate increase of uptake during glucose infusion. We conclude that increases in HGP and HTGO and a decrease of MCR are characteristic features of mild type II diabetes and are more pronounced during glucose infusion. There is also an increase in hepatic GC, a stopgap that controls changes from glucose production to uptake. Postabsorptively, this limits the increase of HGP and glycemia. In contrast, during glucose infusion, increased GC decreases hepatic glucose uptake and thus contributes to hyperglycemia. Obesity per se did not affect GC. An increase in glucose cycling and turnover indicate hepatic insulin resistance that is observed in addition to peripheral resistance. It is hypothesized that in pathogenesis of type II diabetes, augmented activity of glucose-6-phosphatase and kinase may be of importance.

Adult↗
PubMed1988

Localization of pancreastatin immunoreactivity in porcine endocrine cells.

Pancreastatin is a peptide isolated from the porcine pancreas and shown to inhibit insulin release. We have studied the immunocytochemical distribution of pancreastatin in three porcine endocrine tissues: pancreas, gut, and adenohypophysis. Pancreastatin-specific immunoreactivity was found in all three locations and distributed to numerous cells. In the pancreas, we performed the alternate labeling of consecutive thick (immunofluorescence) or thin (protein A-gold) sections and we observed that pancreastatin colocalizes to secretory granules of insulin and somatostatin-containing cells. The relationship of pancreastatin to chromogranin A is discussed.

APUD Cells↗
PubMed1988

Alpha 2-adrenoceptor blockade does not enhance glucose-induced insulin release in normal subjects or patients with noninsulin-dependent diabetes.

Studies with phentolamine, an alpha-adrenergic antagonist, in normal subjects and diabetic patients have indicated that insulin secretion may be inhibited by tonic alpha-adrenergic stimulation of pancreatic B-cells. We evaluated, with the use of the highly selective alpha 2-adrenoceptor antagonist idazoxan, the role of alpha 2-adrenergic receptors in the regulation of glucose-induced insulin secretion. A glucose infusion test (GIT) was performed after the administration of idazoxan or placebo in normal men (n = 15) and men with noninsulin-dependent diabetes mellitus (n = 6). The normal men were divided into two groups on the basis of high (n = 8) and low (n = 7) insulin responses to prior GITs. The blood glucose and plasma insulin and C-peptide responses to the GIT were similar after idazoxan (40 mg, orally) or placebo treatment in all three groups, although the responses differed among the groups. In the diabetic group iv administration of idazoxan 20 min before the GIT did not alter the insulin response to the GIT. We conclude that alpha 2-adrenergic blockade does not affect glucose-induced insulin secretion in normal men, nor does it improve the impaired first phase of insulin secretion in low insulin responders and noninsulin-dependent diabetes mellitus patients. Phentolamine probably stimulates insulin secretion by a mechanism not involving alpha 2-adrenergic receptors directly.

Adrenergic alpha-Antagonists↗
PubMed1988

Cholecystokinin-33 potentiates and vasoactive intestinal polypeptide inhibits gastric inhibitory polypeptide--induced insulin secretion in the perfused rat pancreas.

Gastric inhibitory polypeptide (GIP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) stimulate insulin secretion. In this study we investigated whether CCK-33 and VIP could influence the insulinogenic effect of simultaneously administered GIP and 6.7 mmol/l glucose in the perfused rat pancreas. We found that at 0.1 nmol/l, GIP markedly potentiated glucose-induced insulin release whereas CCK-33 and VIP had a weak stimulatory effect and only during the late phase. At this low dose level, CCK-33 potentiated but VIP inhibited the late phase of insulin release stimulated by glucose and GIP. At 1.0 nmol/l, GIP, CCK-33, and VIP markedly potentiated both phases of glucose-induced insulin secretion. At this dose level CCK-33 and GIP exerted additive stimulatory effects on the late phase of insulin release triggered by glucose. In contrast, 1.0 nmol/l VIP inhibited insulin secretion augmented by glucose and GIP. In summary 1) GIP, CCK-33 and VIP all potentiate glucose-induced insulin secretion from the perfused rat pancreas, and 2) CCK-33 potentiates and VIP inhibits GIP-induced insulin secretion. We suggest that interactions of this kind are of importance for the precise regulation of insulin secretion.

Animals↗
PubMed1987

Glucose-induced insulin response and insulin sensitivity is not related to HLA-type but to age in young siblings of type 1 (insulin-dependent) diabetic patients.

Glucose-induced insulin response and insulin sensitivity were studied in 32 HLA-identical, 38 haplo-identical and 24 non-identical, islet-cell-antibody-negative, healthy siblings of young Type 1 (insulin-dependent) diabetic patients (age range 10-28 years). No significant differences were obtained between HLA-identical, HLA-haplo-identical siblings and HLA-non-identical siblings in insulin response using an i.v. glucose infusion test even when the insulin sensitivity as estimated by the somatostatin-insulin-glucose infusion test was taken into account. A significant inverse correlation to age was found for both insulin response (r = -0.24, p = 0.02) and insulin sensitivity (r = -0.36, p less than 0.01) in the young siblings studied.

Adolescent↗
PubMed1987

Studies of high and low insulin responders with the hyperglycemic clamp technique.

We have investigated insulin responsiveness in relation to insulin sensitivity during sequential hyperglycemic clamping in low insulin responders (LIR), high insulin responders (HIR) and in women with a history of gestational diabetes (GD). Designation of HIR and LIR was done on the basis of mathematical modeling of the insulin response to a glucose infusion test. Insulin sensitivity was determined by a somatostatin-insulin-glucose infusion test (SIGIT) according to which LIR were subdivided into groups with higher or lesser sensitivity. Hyperglycemic clamping (60 min, 11 mmol/L of glucose) induced diphasic insulin and C-peptide responses in all groups. Insulin and C-peptide responses were significantly higher in HIR than in other groups. The ratio of first phase to total insulin response was higher in HIR v GD but did not differ between other groups. A second identical clamp was performed after a 60-minute rest period. Except in HIR, insulin levels attained were then moderately but significantly higher than during the first clamp. Conversely, the glucose utilization (mg/kg/min) to insulin (mU/L) = M/L ratio was markedly increased in LIR with high insulin sensitivity but not in other groups. We conclude that (1) large and consistent differences exist in glucose-induced insulin secretion from the pancreas between nondiabetic subjects; (2) time dynamics of insulin secretion and priming effects of glucose are similar in LIR with lesser and higher sensitivity; and (3) in the latter group a glucose stress affects insulin sensitivity more markedly than insulin responsiveness.

Blood Glucose↗
PubMed1987

Diabetogenic action of GH and cortisol in insulin-dependent diabetes mellitus. Aspects of the mechanisms behind the Somogyi phenomenon.

The effect on glucose homeostasis of a transient elevation of plasma growth hormone (GH) and cortisol was studied over 6 h in 14 male patients with insulin-dependent diabetes mellitus (IDDM) by using an i.v. somatostatin (100 micrograms/h) - insulin (0.4 mU/kg/min) glucose (3 mg/kg/min) - infusion test (SIGIT). GH (20 mU/kg) was given as a 60 min i.v. infusion during the initial SIGIT period raising the plasma GH level to about 40 micrograms/l, and returning to low basal within 3 h. ACTH (0.1 mg) was given as an i.v. bolus injection at the start of the SIGIT, resulting in plasma cortisol peak values of about 900 nmol/l within 2-3 h. GH raised blood glucose after a lag of 4 h while ACTH alone had no effect. However, ACTH added to GH enhanced the diabetogenic effect of GH. It is concluded that an episodic increase in circulating GH-cortisol, resembling the responses of these hormones to an insulin-induced hypoglycemia, exerts a diabetogenic effect in IDDM-patients not deprived of insulin. While GH is essential in this respect the diabetogenic effect of cortisol is evident only in conjunction with GH.

Adrenocorticotropic Hormone↗
PubMed1987

Effect of thyroid hormones on the activity of hepatic glucose-6-phosphatase in fed and fasted rats.

The action of thyroid hormones on hepatic glucose-6-phosphatase was studied in rats. Fed and 24-h fasted rats received T3 (10 micrograms/day) or T4 (25 micrograms/day) 1 h, 1 or 3 days before sacrificing. In addition a group of fed rats was treated with T4 for 7 and 14 days. The glucose-6-phosphatase activity was measured in the isolated microsomes prepared from the liver. The intactness of the microsomal preparation was checked using 2 mM mannose-6-phosphate as a substrate. In fed rats a single injection of T3 or T4 augmented the activities of the translocase and hydrolase components of glucose-6-phosphatase provided that the rats were killed 24 h after the administration of hormone. This effect was more pronounced in animals treated for 3-14 days. As expected, fasting per se increased the activities of both components of the enzyme. Moreover, in fasted rats treatment with T3 and T4 for 3 days further augmented the activities of the translocase and the hydrolase components of glucose-6-phosphatase. In fed animals T3 and T4 increased the latency of the enzyme whereas in fasted animals thyroid hormones increased the activities of the translocase and hydrolase components in parallel, maintaining the level of latency of the enzyme system. Administration of T3 and T4 increased blood glucose level in fasted rats after one day, while in fed rats a significant hyperglycaemia appeared after 7-14 days of treatment. In conclusion, T3 and T4 increase the activities of the translocase and hydrolase components of hepatic glucose-6-phosphatase in fed and fasted rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Elevated somatostatin in pancreatic islets of adrenalectomized dogs.

We have observed both hyperglucagonemia and hypoinsulinemia in adrenalectomized (Adx) dogs. To determine whether these hormonal alterations are related to changes in distribution of islet hormones in the pancreas, we examined the concentration and total mass of insulin, glucagon, and somatostatin in the head, body, and tail of the pancreas by immunoassay and immunocytochemistry. We studied 6 normal dogs, 5 Adx dogs deprived of cortisol for 24 h (Adx I) and 5 for 48-72 h (Adx II). In normal dogs, single and double immunocytochemical staining showed that, in contrast to some other species, B (insulin) cells are mostly in the central region of islet, whereas A (glucagon) and D (somatostatin) cells are distributed randomly. This topographic distribution was not altered by adrenalectomy. In normal dogs, insulin concentration (micrograms per g) and total mass (micrograms) were higher in the tail (174 +/- 22, 2001 +/- 396) and body (165 +/- 22, 2850 +/- 600) than in the head (91 +/- 17, 668 +/- 156) of pancreas. Glucagon concentration (micrograms per g) and total mass (micrograms) were 17 +/- 2, 178 +/- 17 in the tail; 9.5 +/- 2, 158 +/- 32 in the body, and negligible (0.78 +/- 0.32, 7 +/- 3) in the head, whereas somatostatin concentration (micrograms per g) and total mass (micrograms) were 0.58 +/- 0.26, 4.20 +/- 1.5 in the T, 0.23 +/- 0.10, 3.9 +/- 1.6 in the B, and 0.22 +/- 0.05, 1.8 +/- 0.6 in the H. The striking finding was that adrenalectomy caused large increases in somatostatin in all three regions of pancreas in both Adx I and Adx II. The total mass of somatostatin in Adx I and Adx II increased 4-fold in the tail (P less than 0.02-0.005), 5-fold in the body (P less than 0.01-0.001), and 7-9-fold in the head (P less than 0.05-0.005) and concentration increased 6-fold in the body (P less than 0.005) and 7- to 8-fold in the head (P less than 0.01-0.001). There were no significant changes in the content of insulin and glucagon after adrenalectomy. Plasma concentration of glucagon increased by 50% in Adx I (P less than 0.005) and 70% in Adx II (P less than 0.02), insulin decreased by 39% (P less than 0.005), 23% (NS), respectively, and somatostatin increased by 258% (P less than 0.001) in Adx II. Thus the adrenal glands appear to play an important role in regulation of the content of somatostatin in pancreatic islets.

Adrenalectomy↗
PubMed1986

Neuropeptide Y, enkephalin and noradrenaline coexist in sympathetic neurons innervating the bovine spleen. Biochemical and immunohistochemical evidence.

The subcellular distribution of noradrenaline (NA), neuropeptide Y (NPY), Met- and Leu-enkephalin (ENK), substance P (SP), somatostatin (SOM), and vasoactive intestinal polypeptide (VIP) was investigated in homogenates of bovine splenic nerve. The distribution of noradrenergic peptide-containing nerves in the bovine celiac ganglion, splenic nerve and terminal areas in spleen was studied by indirect immunofluorescence histochemistry using antisera to tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), NPY, enkephalin peptides, SP, SOM, VIP, and peptide HI (PHI). After density gradient centrifugation, high levels of NPY- and ENK-like immunoreactivity (LI) were found in high-density gradient fractions, coinciding with the main NA peak. SP, SOM and VIP were found in fractions with a lower density, VIP being also enriched in a heavy fraction; the latter three peptides were present in low concentrations. Immunohistochemistry revealed that staining for NPY-LI and ENK-LI partly overlapped that for TH and DBH in celiac ganglia, splenic nerve axons and terminal areas of spleen. Almost all principal ganglion cells were TH- and DBH-immunoreactive. Many were also NPY-immunoreactive, whereas a smaller number were ENK-positive. In the celiac ganglion patches of dense SP-positive networks and some VIP/PHI- and ENK-immunoreactive fibers were seen around cell bodies. The results indicate that NPY and ENK are stored with NA in large dense-cored vesicles in unmyelinated axons of bovine splenic nerve. SP, SOM and VIP appear in different organelles in axon populations separate from sympathetic noradrenergic nerves.

Adrenergic Fibers↗
PubMed1986

Glucose uptake and binding of digoxin to skeletal muscle.

Physical exercise induces increased uptake of both digoxin and glucose in exercising skeletal muscle. Glucose uptake could be a regulatory factor for the digoxin binding to skeletal muscle, since in dogs, insulin and glucose infusion have been reported to increase the uptake of digoxin in muscle. In the present study on eight healthy digitalized subjects (0.5 mg digoxin daily) the uptake of glucose in skeletal muscle was achieved by infusion of 6 mg/kg body weight/min glucose, 0.004 IE/kg body weight/min insulin and 300 micrograms/h somatostatin. Serum and skeletal muscle digoxin levels were analysed before and during the infusion. We found no changes in the digoxin levels in serum and skeletal muscle in spite of an increased uptake of glucose in the muscle. Thus, glucose uptake in skeletal muscle is probably not an important regulatory factor for the change in muscle digoxin binding induced by exercise.

Adult↗
PubMed1986

Nutritional status and endocrine response to hemorrhage.

Hyperglycemia-inducing hyperosmolality has recently been proven beneficial in the maintenance of blood volume and extracellular fluid volume during early hemorrhagic hypotension. Fed animals benefitted from better plasma refill compared with starved ones when subjected to equal blood loss. Using lightly sedated fed and 24-30 h starved rats, hormones with relevance to glucose homeostasis were studied during 90 min of hemorrhagic hypotension of 70 mmHg (1 mmHg = 133.32 Pa). Marked differences in the overall hormonal developments were found between the two groups. In fed rats, insulin and glucagon responses were initially attenuated, while somatostatin increased to an early peak level at 30 min, returning to basal at 90 min. In starved rats, somatostatin increased gradually during the 90 min. Adrenaline release was massive in both groups. Corticosterone showed no increase from basal levels in the fed group during hemorrhage, while starved rats increased their basal level fourfold already at 30 min. These data are presented as evidence that changing nutritional status alters hormonal response to hypovolemic stress.

Animals↗
PubMed1985

New probes to study insulin resistance in men; futile cycle and glucose turnover.

Insulin resistance has been measured in man by nonsteady state tracer methodology. Increase in overall glucose utilization and suppression of glucose production was measured when hyperglycemia was achieved either by infusing glucagon or glucose. With the first method, insulin resistance was assessed in obese man and in lean hypertriglyceridemic patients. With the second method, insulin resistance was assessed in lean mild type II diabetics. These methodologies can only assess deficiences in overall glucose utilization and glucose production, but cannot delineate the defect in glucose uptake by the liver. However, if a given metabolic event is essentially characteristic of only one organ, metabolic abnormalities specific to that organ can be detected in vivo provided there is a probe specific to that metabolic pathway. Therefore, in lean mild type II diabetics the liver glucose futile cycle was assessed by a double tracer method. Previously it was shown that liver glucose futile cycling is increased in diabetic dogs. In healthy control subjects in basal state and during glucose infusion, the futile cycle could not be detected, but it represented a major part of glucose metabolism in liver of type II diabetics. It appears, therefore, that most of the glucose taken up by the liver during the glucose challenge in diabetics reenters the blood stream without being oxidized or polymerized. On the basis of these studies, it was concluded that excessive hyperglycemia in the diabetics during glucose infusion is due to a decrease in irreversible glucose uptake (impaired phosphorylation and futile cycling) and to a decrease in suppression of glucose production. The relative contribution of the liver and periphery to hyperglycemia seems to be almost equivalent. The mechanism behind the increased glucose cycle activity is not clear. It may be due to a relative decrease of glycogen synthase or increase in glucose-6-phosphatase or both. These observations in mild lean type II diabetics may have implications also in some other types of diabetes, since we have observed that futile cycling is even more marked in obese type II diabetics and that it could account in part for the diabetogenic effect of growth hormone in acromegalics.

Blood Glucose↗