Abnormalities of insulin responses after ambient and previous exposure to glucose in streptozocin-diabetic and dexamethasone-treated rats. Role of hyperglycemia and increased B-cell demands.
In NIDDM, B-cells are insensitive to glucose. We studied the specificity and evolution of this abnormality in 6-10-wk-old neonatally streptozocin-diabetic (STZ) and in dexamethasone-treated (DMT) rats. Not only the effect of ambient but also that of previous glucose (priming effect) was characterized in the perfused pancreas. In fed STZ, blood glucose was elevated to 9.2 +/- 0.8 versus 5.3 +/- 0.2 mM in control (C) rats. Ambient glucose (27 mM) in the perfusate induced a significant but reduced total response (11% of C) that was predominantly monophasic. Secretion was promptly induced (in less than 20 s) both in STZ and C. Other nutrients, i.e., glyceraldehyde (10 mM) and alpha-ketoisocaproic acid (KIC) (5 mM) also induced reduced and monophasic responses, whereas, in contrast, 3-isobutyl-1-methylxanthine (IBMX) induced an enhanced response that was 3.8-fold larger than in C. In DMT, blood glucose was normal (5.4 +/- 0.3 mM). Ambient glucose (27 mM) in the perfusate induced a normal first phase and a moderately reduced second phase (52% of untreated rats). DMT rats were hyperresponsive to IBMX, this agent inducing 2.5-fold higher release than in untreated rats. Previous perfusion with 27 mM glucose enhanced twofold the effect of a second stimulation period with glucose in C. This induction of priming by glucose could not be demonstrated in fed STZ or in DMT. However, when STZ were fasted or insulin treated for 36 h, induction of priming reappeared, i.e., the second pulse of glucose evoked 2-3-fold more insulin release than the first pulse.(ABSTRACT TRUNCATED AT 250 WORDS)
Grill
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Rundfeldt
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005985:Glyceraldehyde / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000032:analysis / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007651:Keto Acids / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D007651:Keto Acids; D005985:Glyceraldehyde; D003907:Dexamethasone; C013082:alpha-ketoisocaproic acid; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine